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7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

Purpose: To assess the fracture resistance and failure mode of endodontically treated premolars reconstructed by different preparation approaches: cervical margin relocation (CMR) and crown lengthening (CL) with complete ferrule (CLF) and partial ferrule (CLPF) with three different post and core systems., Materials and Methods: In this in vitro study, 100 maxillary premolars were assigned to the following 10 groups according to their preparation approach and type of post and core system (n = 10): (I) control (intact teeth), (II) prefabricated fiber post (PFP) and composite core with CMR (PFP-CMR), (III) polyethylene fiber-reinforced composite (PEFRC) with CMR (PEFRC-CMR), (IV) casting post (CP) and core with CMR (CP-CMR), (V) PFP-CLPF, (VI) PEFRC-CLPF, (VII) CP-CLPF, (VIII) PFP-CLF, (IX) PEFRC-CLF, and (X) CP-CLF. After thermomechanical loading, the fracture resistance and failure mode were assessed. Data were analyzed statistically (α = 0.05)., Results: In all post and core systems, the CLPF approach had lower fracture resistance than CMR (p < 0.05); CLF showed higher fracture resistance than CLPF only in the PFP system (p = 0.038). In PEFRC and CP systems, the difference between CLF and CLPF was not significant (p > 0.05). No significant difference was found in fracture resistance of different post and core systems with the same preparation approach (p > 0.05). CLPF showed the highest frequency of favorable, and CLF showed the highest frequency of unfavorable fractures., Conclusion: CLPF yielded lower fracture resistance than CMR. The difference in fracture resistance was not significant between CLF and CMR but the frequency of unfavorable fractures was higher in CLF than in other groups., (© 2023 by the American College of Prosthodontists.)

Aim: To determine the effects of RVX-208, a selective bromodomain and extra-terminal domain (BET) inhibitor targeting bromodomain 2 (BD2), on periodontal inflammation and bone loss., Materials and Methods: Macrophage-like cells (RAW264.7) and human gingival epithelial cells were challenged by Porphyromonas gingivalis (Pg) with or without RVX-208. Inflammatory gene expression and cytokine production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RAW264.7 cells were induced to osteoclast differentiation. After RVX-208 treatment, osteoclast differentiation was evaluated by histology, tartrate-resistant-acid-phosphatase (TRAP) activity and the expression of osteoclast-specific genes. The effect of RVX-208 on osteoclast transcriptome was studied by RNA sequencing. Periodontitis was induced in rats by ligature and local RVX-208 treatment was administered every other day. Alveolar bone loss was measured by micro-computed tomography., Results: RVX-208 inhibited inflammatory gene expression and cytokine production in Pg-infected cells. Osteoclast differentiation was inhibited by RVX-208, as evidenced by reduced osteoclast number, TRAP activity and osteoclast-specific gene expression. RVX-208 displayed a more selective and less profound suppressive impact on transcriptome compared with pan-BET inhibitor, JQ1. RVX-208 administration prevented the alveolar bone loss in vivo., Conclusions: RVX-208 regulated both upstream (inflammatory cytokine production) and downstream (osteoclast differentiation) events that lead to periodontal tissue destruction, suggesting that it may be a promising 'epi-drug' for the prevention of periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is associated with a poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph-like ALL are largely unknown. We conducted a single-center retrospective analysis of adult patients (n = 96) with r/r B-ALL and fusions associated with Ph-like who received novel salvage therapies. Patients were treated with 149 individual novel regimens (blinatumomab = 83, inotuzumab ozogamicin [InO] = 36, and CD19CAR T cells = 30). The median age at first novel salvage therapy was 36 years (range; 18-71). Ph-like fusions were IGH::CRLF2 (n = 48), P2RY8::CRLF2 (n = 26), JAK2 (n = 9), ABL-class (n = 8), EPOR::IGH (n = 4) and ETV6::NTRK2 (n = 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (p < .001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (p = .002). Blinatumomab was administered at an older age compared to InO and CAR T-cells (p = .004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (p = .044) and pretreatment marrow blasts (p = .006) predicted the CR/CRi rate, while the Ph-like fusion subtype (p = .016), pretreatment marrow blasts (p = .022) and post-response consolidation with alloHCT (p < .001) influenced event-free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph-like ALL and successfully transitioning the responders to alloHCT., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: In dental education, students must learn to integrate and coordinate complex knowledge, skills and attitudes and to transfer this learning to clinical practice. One major issue of concern in education in general and dental education, in particular, is to fill the gap between knowledge and practice., Methods: The purpose of this study was to explore the problems that dental students have in transferring knowledge from the classroom to the real clinical setting. More specifically, we investigated the factors that complicate clinical management and clinical reasoning for these novices, including their common errors, in order to design an educational simulation programme in primary teeth pulpotomy. To this end, we conducted 16 semi-structured interviews with experts and novices, performing a thematic analysis of the data obtained. All interviews were audio recorded and transcribed verbatim., Results: For each major skill-clinical management and clinical reasoning-we identified complicating factors and common errors that related to the child (the patient), parents and dental student (the three main themes). For each theme, we identified further sub-themes., Conclusion: The data obtained provided valuable insights into the factors that affect dental students' performance on clinical management and clinical reasoning in primary teeth pulpotomy., (© 2021 The Authors. European Journal of Dental Education published by John Wiley & Sons Ltd.)

Aims: The purpose of this study was to assess the antiviral activity of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination and to describe the pharmacokinetics of rilpivirine and its association with resistance in clinical routine., Methods: A retrospective multicentre cohort study was performed in both naive and pretreated HIV patients receiving the once-daily rilpivirine/emtricitabine/tenofovir disoproxil fumarate regimen. Immuno-virologic and resistance data, and rilpivirine plasma trough concentrations were collected over the follow-up. Statistical analyses were performed to evaluate the relationship between rilpivirine pharmacokinetics and virological response. Receiver operating characteristic (ROC) curve analysis was performed to determine the best target rilpivirine trough concentration., Results: Overall, 379 patients were included. After a median follow-up of 28 months, 26% of patients discontinued mainly due to toxicity and the virological success rate was 65.7%. Virological failure occurred in 5% of patients. A significant proportion of patients with HIV-RNA > 40 copies/mL displayed rilpivirine plasma trough concentrations below the currently used 50 ng/mL efficacy threshold at both M6 (28%) and M12 (31%), in agreement with a significant lower median rilpivirine plasma trough concentration compared with patients virologically suppressed. Half of the patients with virologic failure who acquired rilpivirine resistance mutations had at least one suboptimal rilpivirine trough concentration. The optimal target for rilpivirine trough concentration was 70 ng/mL (sensitivity 75.4%; specificity 61.5%)., Conclusions: This study shows the impact of rilpivirine plasma trough concentration on both virological response and the emergence of rilpivirine mutations. Moreover, our results suggest that a higher target of rilpivirine trough concentration could be proposed in clinical practice., (© 2020 The British Pharmacological Society.)

The fetal sheep model has served as a biologically relevant and translational model to study in utero haematopoietic stem cell transplantation (IUHSCT), yet little is known about the ontogeny of the bone marrow (BM) niches in this model. Because the BMmicroenvironment plays a critical role in the outcome of haematopoietic engraftment, we have established the correlation between the fetal-sheep and fetal-human BM niche ontogeny, so that studies addressing the role of niche development at the time of IUHSCT could be accurately performed. Immunofluorescence confocal microscopic analysis of sheep fetal bone from gestational days (gd) 25-68 showed that the BM microenvironment commences development with formation of the vascular niche between 25 and 36 gd in sheep; correlating with the events at 10-11 gestational weeks (gw) in humans. Subsequently, between 45 and 51 gd in sheep (c. 14 gw in humans), the osteoblastic/endosteal niche started developing, the presence of CD34(+)  CD45(+) cells were promptly detected, and their number increased with gestational age. IUHSCT, performed in sheep at 45 and 65 gd, showed significant haematopoietic engraftment only at the later time point, indicating that a fully functional BM microenvironment improved engraftment. These studies show that sheep niche ontogeny closely parallels human, validating this model for investigating niche influence/manipulation in IUHSCT engraftment., (© 2014 John Wiley & Sons Ltd.)