PKCζ-Mitogen-Activated Protein Kinase Signaling Mediates Crotalphine-Induced Antinociception.

Crotalphine (CRP) is a structural analogue to a peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. This peptide induces a potent and long-lasting antinociceptive effect that is mediated by the activation of peripheral opioid receptors. The opioid receptor activation regulates a variety of intracellular signaling, including the mitogen-activated protein kinase (MAPK) pathway. Using primary cultures of sensory neurons, it was demonstrated that crotalphine increases the level of activated ERK1/2 and JNK-MAPKs and this increase is dependent on the activation of protein kinase Cζ (PKCζ). However, whether PKCζ-MAPK signaling is critical for crotalphine-induced antinociception is unknown. Here, we biochemically demonstrated that the systemic crotalphine activates ERK1/2 and JNK and decreases the phosphorylation of p38 in the lumbar spinal cord. The in vivo pharmacological inhibition of spinal ERK1/2 and JNK, but not of p38, blocks the antinociceptive effect of crotalphine. Of interest, the administration of a PKCζ pseudosubstrate (PKCζ inhibitor) prevents crotalphine-induced ERK activation in the spinal cord, followed by the abolishment of crotalphine-induced analgesia. Together, our results demonstrate that the PKCζ-ERK signaling pathway is involved in crotalphine-induced analgesia. Our study opens a perspective for the PKCζ-MAPK axis as a target for pain control.

Coral microbiome manipulation elicits metabolic and genetic restructuring to mitigate heat stress and evade mortality.

Beneficial microorganisms for corals (BMCs) ameliorate environmental stress, but whether they can prevent mortality and the underlying host response mechanisms remains elusive. Here, we conducted omics analyses on the coral Mussismilia hispida exposed to bleaching conditions in a long-term mesocosm experiment and inoculated with a selected BMC consortium or a saline solution placebo. All corals were affected by heat stress, but the observed "post-heat stress disorder" was mitigated by BMCs, signified by patterns of dimethylsulfoniopropionate degradation, lipid maintenance, and coral host transcriptional reprogramming of cellular restructuration, repair, stress protection, and immune genes, concomitant with a 40% survival rate increase and stable photosynthetic performance by the endosymbiotic algae. This study provides insights into the responses that underlie probiotic host manipulation. We demonstrate that BMCs trigger a dynamic microbiome restructuring process that instigates genetic and metabolic alterations in the coral host that eventually mitigate coral bleaching and mortality.

Microbial communities in anaerobic digesters change over time and sampling depth.

Anaerobic digestion (AD) is a process resulting from the anaerobic metabolism of specific microorganisms that produce an eco-friendly type of energy and a stabilized soil fertilizer. We described the microbial communities and their changes in three depths of BioKöhler® biodigester, fed with cattle manure for 18 days, under anaerobic incubation at the psychrophilic temperature range (~ 20 °C). During the experiment, the maximum methane content in the raw biogas was 79.9%. Non-metric multidimensional scaling (MDS) showed significant differences among microbial communities in the bottom, medium, and upper depths. Considering all the periods of incubation, the microbial communities changed until the eighth day, and they remained stable from eighth to seventeenth days. Bacteroidetes, Firmicutes, and Synergistetes were the most abundant phyla in samples, representing approximately 41% of the total OTUs. The relative abundance of the phyla Euryarchaeota, Actinobacteria, Firmicutes, and Verrucomicrobia changed from bottom to medium sampling points. Moreover, Crenarchaeota differed in frequencies from medium to upper, and Acidobacteria from bottom to upper samples. Lentisphaerae, Chloroflexi, and LD1 were different solely at the bottom, whereas OP9 and Tenericutes only in the medium. Psychrophilic AD performed in this work removed pathogens like Salmonella and Escherichia, as observed at the digestate analyzed. This type of treatment of raw manure besides producing eco-friendly energy efficiently also generates a stabilized and safe biomass that can be used as fertilizer in soils.

Influence of scanner, powder application, and adjustments on CAD-CAM crown misfit.

STATEMENT OF PROBLEM: The manufacturers of computer-aided design and computer-aided manufacturing (CAD-CAM) systems emphasize that new technologies can improve the marginal fit of dental crowns. However, data supporting this claim are limited. PURPOSE: The purpose of this in vitro study was to investigate the differences among the following fabrication methods on the marginal discrepancy of dental crowns: intraoral optical scanners, powder application, and adjustments of intaglio surface. MATERIAL AND METHODS: A single human premolar was fixed on a typodont and prepared to receive crowns prepared by the CEREC CAD-CAM system. Three fabrication techniques were used: digital scans using the CEREC Bluecam scanner with titanium dioxide powder (TDP), digital scans using the CEREC Omnicam scanner without TDP, and digital scans using the Omnicam scanner with TDP. Five experimental groups (n=10) were designated: Bluecam (group B), Bluecam with adjustments (group BA), Omnicam (group O), Omnicam with adjustments (group OA), and Omnicam with TDP (group OP). The specimens were scanned using microcomputed tomography to measure the vertical, horizontal, and internal fit and volumetric 3-dimensional (3D) internal fit values of each luting space. The paired t test was used to evaluate mean marginal fit change after adjustments within the same group. One-way analysis of variance and post hoc tests were used to compare groups B, O, and OP (α=.05). RESULTS: Mean vertical fit values ±standard deviations of group B=29.5 ±13.2 µm; BA=26.9 ±7.7 µm; O=149.4 ±64.4 µm; OA=49.4 ±12.7 µm; and OP=33.0 ±8.3 µm. Adjustments in the intaglio surface and TDP application statistically influenced the vertical fit of group O (P<.001). The percentage of vertical fit values <75 µm in group B=89.3%, BA=92.7%, O=31.0%, OA=73.5%, and OP=92.0%. Mean horizontal fit values for group B=56.2 ±21.5 µm; 85.8 ±44.4 µm for group BA; 77.5 ±11.8 µm for group O; 102.5 ±16.2 µm for group OA; and 91.4 ±19.4 µm for group OP. Results from group B were significantly different from those of the other test groups (P<.05). The percentages of horizontal misfit were 61.2% in group B; 73.5% in group BA; 88.1% in group O; 92.4% in group OA; and 85.0% in group OP. Volumetric 3D internal fit values in group B were 9.4 ±1.3 mm3; 10.7 ±1.0 mm3 in group BA; 11.8 ±2.1 mm3 in group O; 11.0 ±1.3 mm3 in group OA; and 9.6 ±0.9 mm3 in group OP. The overall results from groups B and OP were better than those of group O, with regard to vertical misfit and volumetric 3D internal fit. CONCLUSIONS: Different intraoral optical scanners, powder application, and internal adjustments influenced the marginal discrepancy of crowns. Crowns fabricated using the Omnicam system had significantly higher vertical discrepancy and volumetric 3D internal fit than those fabricated using the Bluecam scanner with TDP. Adjustments of the intaglio surface improved the vertical fit of crowns made using the Omnicam scanner; however, TDP application before Omnicam scanning improved the vertical fit as well as the volumetric 3D internal fit value of the luting space of crowns.

Bone Remodeling Around Implants with External Hexagon and Morse-Taper Connections: A Randomized, Controlled, Split-Mouth, Clinical Trial.

OBJECTIVES: To evaluate clinical, radiographic, microbiologic, and biomechanical parameters related to bone remodeling around implants with external hexagon (EH) and Morse-taper (MT) connections. MATERIALS AND METHODS: Twelve totally edentulous patients received four custom-made implants in the interforaminal region of the mandible. Two of those implants had the same macroscopic design, but different prosthetic connections. All patients received an immediate implant-supported prosthesis. Clinical parameters (periimplant probing pocket depth (PPD), modified gingival index (mGI), and mucosal thickness (MTh)) were evaluated at 12 months follow-up. The distance between the top of the implant and the first bone-to-implant contact (IT-FBIC) was evaluated on standardized digital peri-apical radiographs acquired at 1, 3, 6, and 12 months follow-up. Samples of the subgingival microbiota were collected 1, 3, and 6 months after implant loading and used for the quantification of Tanerella forsythia, Porphyromonas gingivalis, Aggragatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum. Further, 36 computerized-tomography based finite element (FE) models were accomplished, simulating each patient under three loading conditions. RESULTS: The evaluated clinical parameters were equal for EH and MT implants. Mean IT-FBIC was significantly different between the tested connections (1.17 ± 0.44 mm for EH, and 0.17 ± 0.54 mm for MT, considering all evaluated time periods). No significant microbiological differences could be observed between tested connections. FE analysis showed a significantly higher peak of equivalent (EQV) strain (p = 0.005) for EH (mean 3,438.65 µÎµ) compared to MT (mean 840.98 µÎµ) connection. CONCLUSIONS: Radiographic periimplant bone loss depends on the implant connection type. MT connections showed less periimplant bone loss, compared to EH connections.

Avaliação da estabilidade dos tecidos duros e moles em implantes imediatos com carga imediata em área estética: estudo clínico prospectivo longitudinal / Soft and hard tissue maintenance following placement of immediate-loaded implants in the aesthetic zone: a prospective longitudinal clinical trial

O objetivo desse trabalho foi avaliar, clínica e radiograficamente (bi/tridimensional), as alterações em tecidos moles e duros encontradas após a colocação de implantes imediatos com carga imediata em alvéolos pós-extração. Dez pacientes tratados com implantes imediatos com carga imediata nos incisivos central e lateral superiores foram incluídos. Parâmetros clínicos foram avaliados em fotografias padronizadas tiradas após a instalação do implante ( baseline ) e 1, 3 e 6 meses após. Parâmetros bi- e tridimensionais foram medidos em tomografias Cone-Beam, para avaliar a estabilidade do tecido ósseo na região vestibular. Também foram realizadas análises clínicas e fotográficas dos tecidos moles, para avaliar a sua estabilidade durante o período de avaliação. Não houve variações estatisticamente significativas nos parâmetros clínicos e radiográficos avaliados, tendo sido demonstrada uma manutenção de 94% do volume do osso vestibular. Implantes imediatos com carga imediata apresentam boa estabilidade dos tecidos moles e duros peri-implantares...

To evaluate by clinical and radiographic bi- and tridimensional means the soft and hard tissues alterations following immediate implant placement and loading in postextraction sockets in theanterior maxilla. Ten patients, treated with immediate-loaded implants in the maxillary central or lateral incisors, were evaluated in this study. Clinical parameters were evaluated in standardized pictures taken at baseline (immediately after), and 1, 3, and 6 months after provisional implant-supported single crown placement. Bi- and tridimensional radiographic parameters were evaluated from standardized digital periapical radiographies and from CBCT images. The volume of the buccal bone wall covering the central millimeter of the implant was also assessed in the CBCT images. The variation for all clinical, bi- and tridimensional parameters assessed was non-statistically significant. There was 94% maintenance of bone volume. The parameters assessed showed good clinical, bi- and tridimensional radiographic stability of soft and hard tissues for implants immediately placed and loaded in aesthetic zones...

Remodelação óssea de implantes com conexão hexágono externo e elementos de retenção no módulo da crista sob carregamento imediato – estudo clínico prospectivo longitudinal de um ano / Bone remodeling of implants with external hexagon connection and retention elements at the crestal module under immediate loading – a 1-year longitudinal prospective clinical trial

Objetivo: avaliar a remodelação óssea radiográfica ao redor de implantes hexágono externo (EH) que possuem roscas no módulo da crista. Material e métodos: doze pacientes desdentados totais receberam quatro implantes (Ø 3,8 mm x 13 mm) customizados na região interforaminal. Doze desses implantes foram hexágono externo com roscas no módulo da crista. Todos os pacientes receberam uma prótese implantossuportada imediata. A distância entre o topo do implante e o primeiro contato osso/implante (IT-FBIC) foi avaliada em radiografias periapicais digitais padronizadas adquiridas em um, três, seis e 12 meses de acompanhamento. A comparação entre vários períodos de observação foi realizada utilizando análise de variância (Anova) para medidas repetidas, seguida pelo teste post-hoc de Tukey. Resultados: a variação radiográfica da perda óssea peri-implantar foi significativamente diferente entre os períodos de acompanhamento (p < 0,001). A média de IT-FBIC foi de 1,17 ± 0,44 mm, depois de 12 meses de carregamento funcional. Conclusão: a remodelação óssea peri-implantar ocorrerá para implantes com hexágono externo, independentemente da presença de elementos de retenção no módulo da crista do implante

Objective: to evaluate the radiographic bone remodeling around implants using external hexagon (EH) with a threaded implant crestal module. Material and methods: twelve patients with totally edentulous mandibles received four custom-made (Ø 3.8 x 13 mm) implants in the interforaminal region. Twelve of the implants were external hexagon with a threaded implant crestal module. All patients received an immediate implant-supported prosthesis. The distance between the top of the implant and the first bone-to-implant contact (IT-FBIC) was evaluated on standardized digital periapical radiographs acquired at one, three, six, and 12 months of follow-up. Comparison among multiple observation periods was performed using repeated-measures analysis of variance (Anova), followed by a Tukey post-hoc test. Results: the radiographic periimplant bone loss was significantly different among the follow-up periods (p < 0.001). Mean IT-FBIC was 1.17 mm ± 0.44 mm, at 12 months follow-up period. Conclusions: radiographic periimplant bone remodeling will occur for implants using external hexagon, regardless of the presence of retention elements at the implant crestal module.