Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons and are activated by agonists of protease-activated receptor 2

Serine proteases generated during injury and inflammation cleave protease-activated receptor 2 (PAR(2)) on primary sensory neurons to induce neurogenic inflammation and hyperalgesia. Hyperalgesia requires sensitization of transient receptor potential vanilloid (TRPV) ion channels by mechanisms involving phospholipase C and protein kinase C (PKC). The protein kinase D (PKD) serine/threonine kinases are activated by diacylglycerol and PKCs and can phosphorylate TRPV1. Thus, PKDs may participate in novel signal transduction pathways triggered by serine proteases during inflammation and pain. However, it is not known whether PAR(2) activates PKD, and the expression of PKD isoforms by nociceptive neurons is poorly characterized. By using HEK293 cells transfected with PKDs, we found that PAR(2) stimulation promoted plasma membrane translocation and phosphorylation of PKD1, PKD2, and PKD3, indicating activation. This effect was partially dependent on PKCepsilon. By immunofluorescence and confocal microscopy, with antibodies against PKD1/PKD2 and PKD3 and neuronal markers, we found that PKDs were expressed in rat and mouse dorsal root ganglia (DRG) neurons, including nociceptive neurons that expressed TRPV1, PAR(2), and neuropeptides. PAR(2) agonist induced phosphorylation of PKD in cultured DRG neurons, indicating PKD activation. Intraplantar injection of PAR(2) agonist also caused phosphorylation of PKD in neurons of lumbar DRG, confirming activation in vivo. Thus, PKD1, PKD2, and PKD3 are expressed in primary sensory neurons that mediate neurogenic inflammation and pain transmission, and PAR(2) agonists activate PKDs in HEK293 cells and DRG neurons in culture and in intact animals. PKD may be a novel component of a signal transduction pathway for protease-induced activation of nociceptive neurons and an important new target for antiinflammatory and analgesic therapies.

Training pharmacists to deliver a complex information technology intervention (PINCER) using the principles of educational outreach and root cause analysis

Objective: To describe the training undertaken by pharmacists employed in a pharmacist-led information technology-based intervention study to reduce medication errors in primary care (PINCER Trial), evaluate pharmacists’ assessment of the training, and the time implications of undertaking the training. Methods: Six pharmacists received training, which included training on root cause analysis and educational outreach, to enable them to deliver the PINCER Trial intervention. This was evaluated using self-report questionnaires at the end of each training session. The time taken to complete each session was recorded. Data from the evaluation forms were entered onto a Microsoft Excel spreadsheet, independently checked and the summary of results further verified. Frequencies were calculated for responses to the three-point Likert scale questions. Free-text comments from the evaluation forms and pharmacists’ diaries were analysed thematically. Key findings: All six pharmacists received 22 hours of training over five sessions. In four out of the five sessions, the pharmacists who completed an evaluation form (27 out of 30 were completed) stated they were satisfied or very satisfied with the various elements of the training package. Analysis of free-text comments and the pharmacists’ diaries showed that the principles of root cause analysis and educational outreach were viewed as useful tools to help pharmacists conduct pharmaceutical interventions in both the study and other pharmacy roles that they undertook. The opportunity to undertake role play was a valuable part of the training received. Conclusions: Findings presented in this paper suggest that providing the PINCER pharmacists with training in root cause analysis and educational outreach contributed to the successful delivery of PINCER interventions and could potentially be utilised by other pharmacists based in general practice to deliver pharmaceutical interventions to improve patient safety.

Simulation of tree-ring widths with a model for primary production, carbon allocation, and growth

We present a simple, generic model of annual tree growth, called "T". This model accepts input from a first-principles light-use efficiency model (the "P" model). The P model provides values for gross primary production (GPP) per unit of absorbed photosynthetically active radiation (PAR). Absorbed PAR is estimated from the current leaf area. GPP is allocated to foliage, transport tissue, and fine-root production and respiration in such a way as to satisfy well-understood dimensional and functional relationships. Our approach thereby integrates two modelling approaches separately developed in the global carbon-cycle and forest-science literature. The T model can represent both ontogenetic effects (the impact of ageing) and the effects of environmental variations and trends (climate and CO2) on growth. Driven by local climate records, the model was applied to simulate ring widths during the period 1958–2006 for multiple trees of Pinus koraiensis from the Changbai Mountains in northeastern China. Each tree was initialised at its actual diameter at the time when local climate records started. The model produces realistic simulations of the interannual variability in ring width for different age cohorts (young, mature, and old). Both the simulations and observations show a significant positive response of tree-ring width to growing-season total photosynthetically active radiation (PAR0) and the ratio of actual to potential evapotranspiration (α), and a significant negative response to mean annual temperature (MAT). The slopes of the simulated and observed relationships with PAR0 and α are similar; the negative response to MAT is underestimated by the model. Comparison of simulations with fixed and changing atmospheric CO2 concentration shows that CO2 fertilisation over the past 50 years is too small to be distinguished in the ring-width data, given ontogenetic trends and interannual variability in climate.

Managing maize under pest species competition: is Bt (Bacillus thuringiensis) maize the solution?

Transgenic crops that contain Cry genes from Bacillus thuringiensis (Bt) have been adopted by farmers over the last 17 years. Unlike traditional broad spectrum chemical insecticides, Bt's toxicity spectrum is relatively narrow and selective, which may indirectly benefit secondary insects that may become important pests. The economic damage caused by the rise of secondary pests could offset some or all of the benefits associated with the use of Bt varieties. We develop a bioeconomic model to analyze the interactions between primary and secondary insect populations and the impact of different management options on insecticide use and economic impact over time. Results indicate that some of the benefits associated with the adoption of genetically engineered insect resistant crops may be eroded when taking into account ecological dynamics. It is suggested that secondary pests could easily become key insect pests requiring additional measures - such as insecticide applications or stacked traits – to keep their populations under the economic threshold.

Ex Vivo Accuracy of an Apex Locator Using Digital Signal Processing in Primary Teeth

The purpose of this study was to evaluate ex vivo the accuracy an electronic apex locator during root canal length determination in primary molars. Methods: One calibrated examiner determined the root canal length in 15 primary molars (total=34 root canals) with different stages of root resorption. Root canal length was measured both visually, with the placement of a K-file 1 mm short of the apical foramen or the apical resorption bevel, and electronically using an electronic apex locator (Digital Signal Processing). Data were analyzed statistically using the intraclass correlation (ICC) test. Results: Comparing the actual and electronic root canal length measurements in the primary teeth showed a high correlation (ICC=0.95) Conclusions: The Digital Signal Processing apex locator is useful and accurate for apex foramen location during root canal length measurement in primary molars. (Pediatr Dent 200937:320-2) Received April 75, 2008 vertical bar Lost Revision August 21, 2008 vertical bar Revision Accepted August 22, 2008

SEM Study of Apical Morphological Alterations in Primary Teeth with Vital and Necrotic Pulps

This study evaluated, by SEM, the morphology of human primary teeth roots. Twenty-four teeth were divided into 3 groups: pulp vitality (group I) and pulp necrosis without (group II) and with apical periodontitis (group III). Roots were analyzed by the presence of periodontal ligament (PDL) fibers and resorption areas. In groups I and II, presence of PDL fibers and absence of resorption were observed in all cases (100%), while all specimens (100%) of group III showed no PDL fibers and resorption areas. In conclusion, there are morphological differences in the apical region of primary teeth with different pulpal and periapical pathologies.

Biofilm on the apical region of roots in primary teeth with vital and necrotic pulps with or without radiographically evident apical pathosis

Aim To evaluate, by scanning electron microscopy (SEM), the presence of biofilms on the external surfaces of the apical third of roots of human primary teeth with vital or necrotic pulps with and without radiographically evident periradicular pathosis. Methodology Eighteen teeth were selected: group I - normal pulp (n = 5), group II - pulp necrosis without radiographic evidence of periapical pathosis (n = 7) and group III - pulp necrosis with well-defined radiographic periapical pathosis (n = 6). After extraction, the teeth were washed with saline and immersed in 0.03 g mL(-1) trypsin solution for 20 min. The teeth were then washed in sodium cacodilate buffer and stored in receptacles containing modified Karnovsky solution. The teeth were sectioned, dehydrated in an ethanol series, critical-point dried with CO(2), sputter coated with gold and the external root surface in the apical third examined by SEM. Results In the teeth of groups I and II, the apical root surfaces were covered by collagen fibres, with no evidence of bacteria (100%). In the teeth of group III, the root apices had no collagen fibres but revealed resorptive areas containing microorganisms (cocci, bacilli, filaments and spirochetes) in all cases (100%). Conclusion Microorganisms organized as biofilms on the external root surface (extraradicular infection) were detected in primary teeth with pulp necrosis and radiographically visible periapical pathosis.

Electronic working length determination in primary teeth by Propex and Digital Signal Processing

The purpose of this study was to evaluate the accuracy of electronic apex locators Digital Signal Processing (DSP) and ProPex, for root canal length determination in primary teeth. Fifteen primary molars (a total of 34 root canals) were divided into two groups: Group I - without physiological resorption (n = 16); and Group II - with physiological resorption (n = 18). The length of each canal was measured by introducing a file until its tip was visible and then it was retracted 1 mm. For electronic measurement, the devices were set to 1 mm short of the apical resorption. The data were analysed statistically using the intraclass correlation coefficient (ICC). Results showed that the ICC was high for both electronic apex locators in all situations - with (ICC: DSP = 0.82 and Propex = 0.89) or without resorption (ICC: DSP = 0.92 and Propex = 0.90). Both apex locators were extremely accurate in determining the working length in primary teeth, both with or without physiological resorption.

Accuracy of the iPex multi-frequency electronic apex locator in primary molars: an ex vivo study

P>Aim To evaluate ex vivo the accuracy of the iPex multi-frequency electronic apex locator (NSK Ltd, Tokyo, Japan) for working length determination in primary molar teeth. Methodology One calibrated examiner determined the working length in 20 primary molar teeth (total of 33 root canals). Working length was measured both visually, with the placement of a K-file 1 mm short of the apical foramen or the most coronal limit of root resorption, and electronically using the electronic apex locator iPex, according to the manufacturers` instructions. Data were analysed statistically using the intraclass correlation (ICC) test. Results Comparison of the actual and the electronic measurements revealed high correlation (ICC = 0.99) between the methods, regardless of the presence or absence of physiological root resorption. Conclusions In this laboratory study, the iPex accurately identified the apical foramen or the apical opening location for working length measurement in primary molar teeth.

Can France really stop them? : A study grounded on the realist perspective about the French foreign policy towards Syria as the root cause of the Phenomenon of French Foreign Fighters

During the Syrian conflict the number of European Foreign Fighters has increased exponentially and has become an ever-growing concern for European policymakers. This phenomenon presents host of major security challenges for European policymakers and governments. Among European countries, France provides the highest number of citizens who have gone to Syria to fight against Assad´s regime. The French authorities have estimated that by mid-2014, over 700 French citizens have left France and travelled to Syria to fight. Historically France has had a relationship with Syria which started with its role as a border-drawing colonial power. Grounded in a framework of realism, that emphasizes nation-states as the primary actor within the international system, the analysis concentrates on the role of France´s foreign policy on the Syria as push factor for terrorism and radicalization. This paper attempts to determinate a specific correlation between the policy that France has been conducting towards Syria between 2000 and 2015, and the phenomenon of French Foreign Fighters. Findings suggest that France´s foreign policy towards Syria is the main root cause of the French Foreign Fighters phenomenon.

Susceptibility of winter crops to Pratylenchus brachyurus and effect on the nematode population in the maize crop

The aim of this study was to evaluate the susceptibility of winter crops to Pratylenchus brachyurus and their effect on the population of phytonematodes in the maize. To study the effect of the plants on nematodes, an experiment was set up in sandy, naturally-infested soil. The area was divided into strips, consisting of six blocks of 16 treatments, with eight winter treatments, subdivided on the basis of the fertilizer used (organic: bird litter, and synthetic: NPK). The initial nematode population was determined by sampling the soil (100 cm(3)) and weeds (10 g of root). The winter treatments put in place (bristle oats, chickpea, vetch bean, common bean, oilseed radish, wheat, intercropped bristle oats + oilseed radish and fallow), and the nematode population determined 100 days after sowing. Subsequently, two maize crops (summer and short season) were planted, and the nematode population in the soil and roots determined during crop full bloom. To evaluate the susceptibility of winter crops to nematodes, an experiment was conducted under controlled conditions, determining the nematode reproduction factor (RF) in the treatments described above. Both in the field and under controlled conditions, it was observed that the bristle oats, oilseed radish and intercropped oats + oilseed radish exhibited lower reproduction rates for P. brachyurus. In the field, lower population of nematodes was observed with the application of bird litter. Under controlled conditions, the highest RF were observed in the fallow plot and under common bean and chickpea, in that order.

Effects on permanent teeth after luxation injuries to the primary predecessors: a study in children assisted at an emergency service

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Immediate reimplantation of primary teeth: a histological study in dogs

Reimplantation of primary teeth has been the subject of various clinical and histological studies, but very little is known about the effect of this treatment on primary teeth. The aim of the present study was to histologically evaluate the biological response of dog primary teeth after immediate reimplantation. Twelve dogs were divided into two groups according to postoperative time: 1 week and 3 weeks. Twenty-one upper and lower intermediate incisors were extracted and submitted to endodontic treatment, reimplantation and splinting. The 21 homologous teeth not submitted to treatment served as controls. The animals were killed after the respective experimental periods, and the obtained specimens were processed for histological analysis. Most dogs of the 1-week group exhibited the following alterations: gingival epithelium was inserted in the cemento-enamel junction, with a small number of chronic inflammatory cells being observed in the gingival corium; the periodontal ligament was partially reestablished, with a more expressive chronic inflammatory infiltrate being observed in the apical third; small root resorption was observed on the palatine/lingual side in the apical third. In contrast, in 3-week animals, gingival epithelial insertion was predominantly absent on the buccal side, and a moderate chronic inflammatory infiltrate was present; the periodontal ligament generally showed no bone-cementum reinsertion especially on the palatine/lingual side, with an expressive inflammatory infiltrate in the apical region, and large root resorption was mainly observed on the palatine and lingual sides. In conclusion, reimplantation causes histological alterations in the tooth and its supporting periodontal structures that suggest the impossibility of its maintenance.

Effect of a calcium hydroxide/chlorhexidine paste as intracanal dressing in human primary teeth with necrotic pulp against Porphyromonas gingivalis and Enterococcus faecalis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of 2 endodontic techniques used to treat human primary molars with furcation radiolucency area: A 48-month radiographic study

Objective: To evaluate 2 techniques for the treatment of human primary molars with necrotic Pulp and bifurcation bone loss by means of radiographic examination for 48 months. Method and Materials: Fifty-one mandibular primary molars were evaluated in children ranging from 4.5 to 6.5 years of age. The teeth with necrotic pulp and bifurcation bone loss were diagnosed by radiographic examination. The teeth were divided into 2 groups: group 1 (28 teeth)-pulpotomy technique using formocresol as a temporary dressing between sessions and coronal chamber obturation with zinc oxide-eugenol cement; and group 2 (23 teeth)-pulpectomy technique with calcium hydroxide paste as a temporary dressing between sessions and root canal obturation with a dense Calcium hydroxide paste. Standardized radiographs were taken immediately after the fillings were completed and after 12, 24, 36, and 48 months. The radiographs were digitized and analyzed with software that outlined and measured the bifurcation radiolucency. Results: Bifurcation radiolucency reduced significantly or repaired completely for both treatnients in the first 12 months. Minor radiographic reduction of the lesion was observed from 12 to 24 months, and no significant reduction of the remaining radioulcent area was observed from 24 to 48 months after treatment. Conclusion: The 2 endodontic techniques evaluated showed similar results. The main effect of treatment on the lesion repair was obtained in the first year after treatment.