Implant-supported fixed and removable prostheses in the fibular mandible

Abstract Background To restore the health-related quality of life (HRQoL) of patients who underwent jaw resection and reconstruction surgery, dental rehabilitation is an essential procedure and also one of the most challenging for oral and maxillofacial surgeons. Even though recent studies have reported the possibility and reliability of dental implant rehabilitation with the fibula free flap (FFF), clinical reports of long-term follow-up cases are scarce. We herein reported seven cases of FFF reconstruction and implant rehabilitation. We also discussed implant planning strategy and surgical techniques. Methods From 2012 to 2019, seven patients were treated with FFF reconstructive jaw surgery combined with dental implant installation and fabrication of implant-supported prostheses at Seoul National University Dental Hospital, Seoul, Korea. Patient characteristics and FFF treatment results were collected. Records of dental implants were analyzed clinically and radiologically. Results Among the seven patients in this report, there were three males and four females, with an average age of 54.4 years. A total of 39 implants were placed in the fibular bone. The mean follow-up period after implant installation was 24 months. Five implants failed and were removed 3 months after installation. The implant success rate was 87.2%. Marginal bone loss at 12 months after loading was 0.23 ± 0.18 mm on the mesial side and 0.25 ± 0.26 mm on the distal side. Conclusion With the challenges present in FFF-reconstructed patients, an implant-supported prosthesis is a reliable option for stable and functional oral rehabilitation. The implant-supported prosthesis on the FFF has great results regarding restoration of function (mastication, swallowing, and speaking), appearance, and overall HRQoL. Collaboration between surgeons and prosthodontists is essential for a satisfying outcome

Clinical feasibility and benefits of a tapered, sand-blasted, and acid-etched surfaced tissue-level dental implant

Abstract Background It has been 50 years since Brånemark first introduced the concept of osseointegration. Since then, numerous ongoing research, developments, and optimization of implant properties have been conducted. Despite the high survival and success rates of dental implants, failures still occur in a small number of patients that are being rehabilitated by implants. The purpose of this study was to evaluate the survival and success rate of the Stella® implants that incorporate sand-blasted and acid-etched (S&E) surface treatment and tapered body design to confirm their clinical feasibility and benefits after placement. Methods We reviewed 61 partially and fully edentulous patients who underwent a tapered, S&E surfaced tissue-level implant placement between May 2013 and February 2016 in the Department of Oral and Maxillofacial Surgery in the Seoul National University Dental Hospital. Patient characteristics and treatment results were collected, and records of dental implants were analyzed clinically and radiologically. Results A total of 105 implant fixtures were placed in these patients. The mean age at the time of the surgery was 63.7 years with a range of 31 to 88 years. In total, 4.0-mm and 4.5-mm diameter implants were the most frequently used dental implants (40%, 49%) in this study. Implants 8.5 mm in length were predominantly used (60%). Seventy dental implants were placed in the mandible (70%), and only one dental implant was placed in the maxillary anterior region. At the end of the 5-year observation period, the success rate of the Stella® implants was 98.1%. Among the 105 implants placed, 2 were considered to be failures. Summarizing the clinical and radiographic results, the remaining 103 implants were considered successfully integrated. Conclusion The overall success rate was 98.1%. The tapered, S&E surfaced tissue-level implant system exhibited great performance in a variety of clinical situations including failed implant sites that enabled predictable and successful treatment outcomes. The effectives of a tapered design of tissue level, not a parallel design, are shown in this clinical report

Peptides Derived from HIV-1 Integrase that Bind Rev Stimulate Viral Genome Integration

The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN), catalyzes the integration of viral DNA into the host cell genome. IN catalyzes the first step of the integration process, namely the 3′-end processing in which IN removes a pGT dinucleotide from the 3′ end of each viral long terminal repeat (LTR). Following nuclear import of the viral preintegration complex, the host chromosomal DNA becomes accessible to the viral cDNA and the second step of the integration process, namely the strand-transfer step takes place. This ordered sequence of events, centered on integration, is mandatory for HIV replication. assay system, we show that INr-1 and INr-2 are able to abrogate the inhibitory effects exerted by Rev and Rev-derived peptides on integrase activity. Both INr-1 and INr-2 were found to be cell-permeable and nontoxic, allowing a study of their effect in HIV-1-infected cultured cells. Interestingly, both INr peptides stimulated virus infectivity as estimated by production of the viral P24 protein, as well as by determination of the appearance of newly formed virus particles. Furthermore, kinetics studies revealed that the cell-permeable INr peptides enhance the integration process, as was indeed confirmed by direct determination of viral DNA integration by real-time PCR.The results of the present study raise the possibility that in HIV-infected cells, the Rev protein may be involved in the integration of proviral DNA by controlling/regulating the activity of the integrase. Release from such inhibition leads to stimulation of IN activity and multiple viral DNA integration events

Perturbation of Host Nuclear Membrane Component RanBP2 Impairs the Nuclear Import of Human Immunodeficiency Virus -1 Preintegration Complex (DNA)

HIV-1 is a RNA virus that requires an intermediate DNA phase via reverse transcription (RT) step in order to establish productive infection in the host cell. The nascent viral DNA synthesized via RT step and the preformed viral proteins are assembled into pre-integration complex (PIC) in the cell cytoplasm. To integrate the viral DNA into the host genome, the PIC must cross cell nuclear membrane through the nuclear pore complex (NPC). RanBP2, also known as Nup358, is a major component of the cytoplasmic filaments that emanates from the nuclear pore complex and has been implicated in various nucleo-cytoplasmic transport pathways including those for HIV Rev-protein. We sought to investigate the role of RanBP2 in HIV-1 replication. In our investigations, we found that RanBP2 depletion via RNAi resulted in profound inhibition of HIV-1 infection and played a pivotal role in the nuclear entry of HIV DNA. More precisely, there was a profound decline in 2-LTR DNA copies (marker for nuclear entry of HIV DNA) and an unchanged level of viral reverse transcription in RanBP2-ablated HIV-infected cells compared to RanBP3-depleted or non-specific siRNA controls. We further demonstrated that the function of Rev was unaffected in RanBP2-depleted latently HIV infected cells (reactivated). We also serendipitously found that RanBP2 depletion inhibited the global ectopic gene expression. In conclusion, RanBP2 is a host factor that is involved in the nuclear import of HIV-1 PIC (DNA), but is not critical to the nuclear export of the viral mRNAs or nucleo-cytoplasmic shuttling of Rev. RanBP2 could be a potential target for efficient inhibition of HIV

In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography

Development of hypoxia-targeted therapies has stimulated the search for clinically applicable noninvasive markers of tumour hypoxia. Here, we describe the validation of [18F]fluoroetanidazole ([18F]FETA) as a tumour hypoxia marker by positron emission tomography (PET). Cellular transport and retention of [18F]FETA were determined in vitro under air vs nitrogen. Biodistribution and metabolism of the radiotracer were determined in mice bearing MCF-7, RIF-1, EMT6, HT1080/26.6, and HT1080/1-3C xenografts. Dynamic PET imaging was performed on a dedicated small animal scanner. [18F]FETA, with an octanol–water partition coefficient of 0.16±0.01, was selectively retained by RIF-1 cells under hypoxia compared to air (3.4- to 4.3-fold at 60–120 min). The radiotracer was stable in the plasma and distributed well to all the tissues studied. The 60-min tumour/muscle ratios positively correlated with the percentage of pO2 values <5 mmHg (r=0.805, P=0.027) and carbogen breathing decreased [18F]FETA-derived radioactivity levels (P=0.028). In contrast, nitroreductase activity did not influence accumulation. Tumours were sufficiently visualised by PET imaging within 30–60 min. Higher fractional retention of [18F]FETA in HT1080/1-3C vs HT1080/26.6 tumours determined by dynamic PET imaging (P=0.05) reflected higher percentage of pO2 values <1 mmHg (P=0.023), lower vessel density (P=0.026), and higher radiobiological hypoxic fraction (P=0.008) of the HT1080/1-3C tumours. In conclusion, [18F]FETA shows hypoxia-dependent tumour retention and is, thus, a promising PET marker that warrants clinical evaluation

Cognitive Performance and Heart Rate Variability: The Influence of Fitness Level

In the present study, we investigated the relation between cognitive performance and heart rate variability as a function of fitness level. We measured the effect of three cognitive tasks (the psychomotor vigilance task, a temporal orienting task, and a duration discrimination task) on the heart rate variability of two groups of participants: a high-fit group and a low-fit group. Two major novel findings emerged from this study. First, the lowest values of heart rate variability were found during performance of the duration discrimination task, compared to the other two tasks. Second, the results showed a decrement in heart rate variability as a function of the time on task, although only in the low-fit group. Moreover, the high-fit group showed overall faster reaction times than the low-fit group in the psychomotor vigilance task, while there were not significant differences in performance between the two groups of participants in the other two cognitive tasks. In sum, our results highlighted the influence of cognitive processing on heart rate variability. Importantly, both behavioral and physiological results suggested that the main benefit obtained as a result of fitness level appeared to be associated with processes involving sustained attention.This research was supported by the Spanish Ministerio de Educación y Cultura with a predoctoral grant (FPU-AP2010-3630) to the first author, Spanish grants SEJ2007-63645 from the Junta de Andalucía to Daniel Sanabria, Mikel Zabala and Esther Morales, and the CSD2008-00048 CONSOLIDER INGENIO (Dirección General de Investigación) to Daniel Sanabria

HIV-1 gp41 and TCRα Trans-Membrane Domains Share a Motif Exploited by the HIV Virus to Modulate T-Cell Proliferation

Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the α-subunit of the T-cell receptor (TCRα). The most striking similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein 41 TMD (gp41 TMD). Previous studies have shown that stable interactions between TCRα and CD3 are localized to this nine amino acid motif within TCRα, and a peptide derived from it (TCRα TMD, GLRILLLKV) interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRα TMD and also from the other two known immunosuppressive regions within gp41

B-Chromosome Ribosomal DNA Is Functional in the Grasshopper Eyprepocnemis plorans

B-chromosomes are frequently argued to be genetically inert elements, but activity for some particular genes has been reported, especially for ribosomal RNA (rRNA) genes whose expression can easily be detected at the cytological level by the visualization of their phenotypic expression, i.e., the nucleolus. The B24 chromosome in the grasshopper Eyprepocnemis plorans frequently shows a nucleolus attached to it during meiotic prophase I. Here we show the presence of rRNA transcripts that unequivocally came from the B24 chromosome. To detect these transcripts, we designed primers specifically anchoring at the ITS-2 region, so that the reverse primer was complementary to the B chromosome DNA sequence including a differential adenine insertion being absent in the ITS2 of A chromosomes. PCR analysis carried out on genomic DNA showed amplification in B-carrying males but not in B-lacking ones. PCR analyses performed on complementary DNA showed amplification in about half of B-carrying males. Joint cytological and molecular analysis performed on 34 B-carrying males showed a close correspondence between the presence of B-specific transcripts and of nucleoli attached to the B chromosome. In addition, the molecular analysis revealed activity of the B chromosome rDNA in 10 out of the 13 B-carrying females analysed. Our results suggest that the nucleoli attached to B chromosomes are actively formed by expression of the rDNA carried by them, and not by recruitment of nucleolar materials formed in A chromosome nucleolar organizing regions. Therefore, B-chromosome rDNA in E. plorans is functional since it is actively transcribed to form the nucleolus attached to the B chromosome. This demonstrates that some heterochromatic B chromosomes can harbour functional genes.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. M. Ruiz-Estévez was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Anti-HIV-1 Response Elicited in Rabbits by Anti-Idiotype Monoclonal Antibodies Mimicking the CD4-Binding Site

Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1. Env-based immunogens inducing such a response could be a major component of future anti-HIV-1 strategies. In this proof-of-concept study we describe the generation of two anti-idiotype (AI) murine antibodies mimicking the CD4bs epitope. Sera were collected from long-term non-progressor patients to obtain CD4bs-directed IgG, through sequential purification steps. The purified IgG were then used as Fab fragments to immunize mice for hybridoma generation. Two hybridomas (P1 and P2), reacting only against the CD4bs-directed IgG, were identified and characterized. The P1 and P2 antibodies were shown to recognize the idiotype of the broadly neutralizing anti-CD4bs human mAb b12. Both P1 and P2 Fabs were able to induce a strong anti-gp120 response in rabbits. Moreover, the rabbits' sera were shown to neutralize two sensitive tier 1 strains of HIV-1 in an Env-pseudotype neutralization assay. In particular, 3/5 rabbits in the P1 group and 1/5 in the P2 group showed greater than 80% neutralizing activity against the HXB2 pseudovirus. Two rabbits also neutralized the pseudovirus HIV-MN. Overall, these data describe the first anti-idiotypic vaccine approach performed to generate antibodies to the CD4bs of the HIV-1 gp120. Although future studies will be necessary to improve strength and breadth of the elicited neutralizing response, this proof-of-concept study documents that immunogens designed on the idiotype of broadly neutralizing Abs are feasible and could help in the design of future anti-HIV strategies