Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development.

BACKGOUND: The potential of a single progenitor cell to establish and maintain long-term protective T-cell immunity in humans is unknown. For genetic disorders disabling T-cell immunity, somatic reversion was shown to support limited T-cell development attenuating the clinical phenotype. However, the cases reported so far deteriorated over time leaving unanswered the important question of long-term activity of revertant precursors and the robustness of the resulting T-cell system. METHODS: We applied TCRß-CDR3 sequencing and mass cytometry on serial samples of a now 18 year-old SCIDX1 patient with somatic reversion to analyse the longitudinal diversification and stability of a T-cell system emerging from somatic gene rescue. FINDINGS: We detected close to 105 individual CDR3ß sequences in the patient. Blood samples of equal size contained about 10-fold fewer unique CDR3ß sequences compared to healthy donors, indicating a surprisingly broad repertoire. Despite dramatic expansions and contractions of individual clonotypes representing up to 30% of the repertoire, stable diversity indices revealed that these transient clonal distortions did not cause long-term repertoire imbalance. Phenotypically, the T-cell system did not show evidence for progressive exhaustion. Combined with immunoglobulin substitution, the limited T-cell system in this patient supported an unremarkable clinical course over 18 years. INTERPRETATION: Genetic correction in the appropriate cell type, in our patient most likely in a T-cell biased self-renewing hematopoietic progenitor, can yield a diverse T-cell system that provides long-term repertoire stability, does not show evidence for progressive exhaustion and is capable of providing protective and regulated T-cell immunity for at least two decades. FUNDING: DFG EH 145/9-1, DFG SCHW 432/4-1 and the German Research Foundation under Germany's Excellence Strategy-EXC-2189-Project ID: 390939984.

New tools for the investigations of Neuro-AIDS at a molecular level: The potential role of data-mining.

Cognitive impairment represents the most significant and devastating neurological complication associated with HIV infection. Despite recent advances in our knowledge of the clinical features, pathogenesis, and molecular aspects of HIV-related dementia, current diagnostic strategies are associated with significant limitations. It has been suggested that the use of some biomarkers may assist researchers and clinicians in predicting the onset of the disease process and in evaluating the effects of new therapies. However, the large number of chemicals and metabolic pathways involved in the pathogenesis of neurodegeneration, warrants the development of novel approaches to integrate this huge amount of data. The contribution of theoretical disciplines, such as bioinformatics and data-mining, may be useful for testing new hypotheses in diagnosis and patient-centered treatment interventions.

Leader genes in osteogenesis: a theoretical study.

Little is still known about the molecular mechanisms involved in the process of osteogenesis. In this paper, the leader genes approach, a new bioinformatics method which has already been experimentally validated, is adopted in order to identify the genes involved in human osteogenesis. Interactions among genes are then calculated and genes are ranked according to their relative importance in this process. In total, 167 genes were identified as being involved in osteogenesis. Genes were divided into 4 groups, according to their main function in the osteogenic processes: skeletal development; cell adhesion and proliferation; ossification; and calcium ion binding. Seven genes were consistently identified as leader genes (i.e. the genes with the greatest importance in osteogenesis), while 14 were found to have slightly less importance (class B genes). It was interesting to notice that the larger part of leader and class B genes belonged to the cell adhesion and proliferation or to the ossification sub-groups. This finding suggested that these two particular sub-processes could play a more important role in osteogenesis. Moreover, among the 7 leader genes, it is interesting to notice that RUNX2, BMP2, SPARC, PTH play a direct role in bone formation, while the 3 other leader genes (VEGF, IL6, FGF2) seem to be more connected with an angiogenetic process. Twenty-nine genes have no known interactions (orphan genes). From these results, it may be possible to plan an ad hoc experimentation, for instance by microarray analyses, focused on leader, class B and orphan genes, with the aim to shed new light on the molecular mechanisms underlying osteogenesis.

Immediate rehabilitation of completely edentulous jaws with fixed prostheses supported by implants placed into fresh extraction sockets and in healed sites: a 4-year clinical evaluation.

PURPOSE: To evaluate the outcome of treatment in the rehabilitation of edentulous jaws with early loaded full-arch screw-retained prostheses after up to 4 years of function. METHODS: Patients with completely edentulous maxillae and/or mandibles, or presenting natural teeth with a poor or hopeless prognosis, received 6 implants each in the mandible and/or 8 in the upper jaw. All patients received a full-arch prosthetic reconstruction. RESULTS: A total of 19 patients were treated with a total of 164 implants. One hundred nineteen implants were placed immediately after tooth extraction, and 45 implants were placed in healed sites. Overall, 8 implants failed, leading to a 4-year cumulative survival rate of 95.1%. CONCLUSIONS: The rehabilitation of the edentulous maxilla and mandible with an early loaded prosthesis represents a viable alternative treatment to classic loading protocols.

A 10-year evaluation of implants placed in fresh extraction sockets: a prospective cohort study.

BACKGROUND: The placement of an implant into a fresh extraction socket has been identified as a reliable technique, allowing a reduction in the time needed for prosthetic rehabilitation. This treatment modality is widely reported in the scientific literature; however, the long-term outcomes and the need for guided bone regeneration (GBR) are still topics of debate. The aim of this prospective study is to evaluate the clinical and radiologic findings from the 10-year follow-up of immediately placed implants, with and without the GBR procedure. METHODS: A total of 159 implants in 91 patients are included in this study; 101 implants required a GBR procedure simultaneously with placement. All implants were used to support a single crown restoration. The clinical/radiographic measurements were repeated each year up to the 10-year follow-up. At the 10-year follow-up visit, the papilla index and the apico-coronal location of mid-buccal soft tissue positions were recorded. RESULTS: The 10-year cumulative success rate was 91.8% (87.9% in the non-GBR group and 94.1% in the GBR group). The clinical attachment level (CAL) measurements were stable throughout the study, and 82% of the implants showed marginal bone loss (MBL) of 0.6 to 1.5 mm at the 10-year visit; moreover, these two parameters did not show significant differences between the GBR and non-GBR groups. Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla. The facial gingival level was more apical in the non-GBR group than in the GBR group (P <0.05). CONCLUSIONS: The present prospective clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate, namely 91.8% after 10 years. No differences were detected in survival and success rate of implants whether GBR procedures were performed or not. The CAL, MBL, and marginal level of soft tissue measurements were stable throughout the 10-year evaluation.

A randomized clinical trial to evaluate and compare implants placed in augmented versus non-augmented extraction sockets: 3-year results.

BACKGROUND: The alveolar ridge undergoes reabsorption and atrophy subsequent to tooth removal and thus exhibits a wide range of dimensional changes. Preservation of the alveolar crest after tooth extraction is essential to enhance the surgical site before implant fixture placement. The aim of this randomized clinical study is to investigate and compare the need for additional augmentation procedures at implant insertion, as well as the success rate and marginal bone loss for implants placed in the grafted sites versus those placed in naturally healed sites. METHODS: Forty patients with ≥1 hopeless tooth were randomly allocated to: 1) a test group, receiving extraction and grafting corticocancellous porcine bone; and 2) a control group, receiving extraction without any graft. After 7 months of healing, implants were inserted in each of the sites. The implants were submerged and loaded after 4 months with metal-ceramic rehabilitation. The follow-up included evaluation of implant diameter and length, the need for additional augmentation procedures at implant placement, implant failure, and marginal bone level changes. All patients were followed over a 3-year period. RESULTS: One implant failed in the control group at the second stage of surgery (6 months after placement); one implant failed in the test group after 2 years of loading. The cumulative implant success rate at the 3-year follow-up visit reached 95% for both groups. No statistically significant differences were detected for marginal bone changes between the two groups. CONCLUSIONS: It was concluded that implants placed into grafted extraction sockets exhibited a clinical performance similar to implants placed into non-grafted sites in terms of implant survival and marginal bone loss. However, grafted sites allowed placement of larger implants and required less augmentation procedures at implant placement when compared to naturally healed sites.

Survival rate for implants placed in the posterior maxilla with and without sinus augmentation: a comparative cohort study.

BACKGROUND: The reduced bone height and proximity of the maxillary sinus are the most common limitations for placement of dental implants in the posterior maxilla. Reconstruction of the atrophic posterior maxilla can be performed with a sinus augmentation procedure. The aim of this cohort study is to compare the survival rate of implants placed in augmented sinus to implants placed in native bone in the posterior maxilla. METHODS: This study was designed as a prospective cohort study and included consecutively treated patients. Patients who required the sinus augmentation (test group) were treated according to the two-stage technique. Patients were scheduled for follow-up evaluation at 3, 6, and 12 months after implant placement and then every 6 months for ≤ 6 years. RESULTS: One hundred and five patients with 393 implants were enrolled in the study. Two hundred and one implants were placed after preliminary sinus floor grafting in 41 patients. The control group contained 64 patients with 192 implants that were placed in pristine bone of the posterior maxilla. The cumulative implant survival rates were 86.1% and 96.4%, respectively. The difference between the two groups was highly significant (P <0.005). CONCLUSIONS: These findings show that implants placed in augmented sinuses had a lower survival rate compared to implants placed in pristine bone. All the implant failures in the augmented sinuses occurred before the prosthetic rehabilitation. Moreover, it should be considered that most of the failures were observed in few patients, thus suggesting cluster behavior.

Implant survival after sinus elevation with Straumann(®) BoneCeramic in clinical practice: ad-interim results of a prospective study at a 15-month follow-up.

OBJECTIVES: Elevation of the sinus floor with Straumann(®) BoneCeramic gave promising results in some recent clinical studies. However, no study has evaluated the long-term survival of implants after this surgical procedure. We are conducting a prospective, observational study to evaluate the long-term implant survival after this surgical procedure in clinical practice. We present here an ad-interim report of this study, including only patients with ≥12-month follow-up after implant placement. METHODS: This prospective cohort study will last until a follow-up of 5 years will be achieved in at least 50 patients. Inclusion criteria are: age ≥18 years; presence of a maxillary partial unilateral or bilateral edentulism involving the premolar/molar areas; elective rehabilitation with oral implants; and physical capability to tolerate conventional surgical and restorative procedures. Patients are treated according to the two-stage technique and the preparation is filled with Straumann(®) BoneCeramic. Implant survival is evaluated every 3 months for the first 2 years, and then every 6 months up to 5 years. RESULTS: Fifteen patients are considered in this ad-interim analysis. Mean follow-up was 14.9 ± 3.1 (range: 6-18 months). In total, three implants failed, in one single patient, 6 months after insertion. The cumulative implant survival rate was 92.5% (95% confidence interval: 83.0-100%). CONCLUSIONS: This ad-interim analysis suggests that the elevation of the sinus floor with Straumann(®) BoneCeramic may be an effective clinical option over >1-year follow-up. A longer term follow-up will allow a deeper characterization of these preliminary findings.

Insertion torque in different bone models with different screw pitch: an in vitro study.

PURPOSE: Orthopedic surgeons use different types of screws for bone fixation. Whereas hard cortical bone requires a screw with a fine pitch, in softer cancellous bone a wider pitch might help prevent micromotion and eventually lead to greater implant stability. The aim of this study was to validate the assumption that fine-pitch implants are appropriate for cortical bone and wide-pitch implants are appropriate for cancellous bone. MATERIALS AND METHODS: Wide-pitch and fine-pitch implants were inserted in both hard (D1 and D2) bone and soft (D3 and D4) bone, which was simulated by separate experimental blocks of cellular rigid polyurethane foam. A series of insertion sites in D1-D2 and D3-D4 experimental blocks were prepared using 1.5-mm and 2.5-mm drills. The final torque required to insert each implant was recorded. RESULTS: Wide-pitch implants displayed greater insertion torque (20% more than the fine-pitch implants) in cancellous bone and were therefore more suitable than fine-pitch implants. CONCLUSION: It is more appropriate to use a fine pitch design for implants, in conjunction with a 2.5-mm osteotomy site, in dense cortical bone (D1 or D2), whereas it is recommended to choose a wide-pitch design for implants, in conjunction with a 1.5-mm osteotomy site, in softer bone (D3 or D4).

Surface roughness of commercial composites after different polishing protocols: an analysis with atomic force microscopy.

BACKGROUND AND AIMS: Polishing may increase the surface roughness of composites, with a possible effect on bacterial growth and material properties. This preliminary in vitro study evaluates the effect of three different polishing systems (PoGo polishers, Enhance, Venus Supra) on six direct resin composites (Gradia Direct, Venus, Venus Diamond, Enamel Plus HFO, Tetric Evoceram, Filtek Supreme XT). MATERIALS AND METHODS: For each composite, 12 square specimens were prepared: 9 specimens were polished, three for each different method, while three specimens were used as controls. Surface roughness was determined with AFM by measuring Root Mean Square (RMS) of average height. RESULTS: PoGo polisher determined a significantly rougher surface, versus controls, in 5 out of 6 composites evaluated. Some significant differences from unpolished controls were observed also for Enhance polishing. Polishing with Venus Supra did not result in any significant difference in surface roughness versus controls. No differences were observed between different polishing systems. CONCLUSIONS: These preliminary results suggest that Venus Supra polishing system could determine a smoother composite surface if compared to the other polishing systems tested. On this basis, we are conducting an in vivo study to evaluate bacterial colonization on some combinations of composites and polishing protocols.

Occlusal features and masticatory muscles activity. A review of electromyographic studies.

OBJECTIVE: Since there is no consensus on the association between occlusion and temporomandibular disorders (TMDs), the aim of the present paper was to conduct a review of electromyographic studies, in order to asses the relationship between various occlusal features and masticatory muscles' activity. MATERIAL AND METHODS: An exhaustive MEDLINE computer search was performed to identify all experimental studies present in the English literature describing the relationship between the electromyographyc evaluation of patients and their occlusal morphology. RESULTS: The search methodology provided a total of 102 abstracts and from these 11 full reports were required as full text. Of the 11 articles selected, 8 studied the variation of the muscular activity as a consequence of the experimental introduction of occlusal disturbances whereas the remaining three studies estimated the electrical muscular characteristics without any artificial alteration of the occlusal morphology. CONCLUSION: The results obtained seem to suggest that occlusal features can affect the electrical signals recordings of masticatory muscles. Further researches are strongly requested to realize if this altered muscular activity can turns in the occurrence of TMDs.

Deep-frozen allogeneic onlay bone grafts for reconstruction of atrophic maxillary alveolar ridges: a preliminary study.

PURPOSE: The purpose of this article was to evaluate the suitability of deep-frozen allograft for ridge augmentation procedures in severely atrophic maxillae and to evaluate the clinical success of dental implants inserted after grafting and before prosthetic rehabilitation. PATIENTS AND METHODS: This study included 13 patients (3 men and 10 women) aged 36 to 65 years. All the patients selected for this study required bone augmentation procedures because of severe alveolar ridge atrophy and were scheduled for onlay bone allograft and titanium implants in a 2-stage procedure. The dental implants were inserted 5 months after grafting. The follow-up period for the implants was 6 months after placement at the second stage of implant surgery. RESULTS: A total of 24 onlay block allografts were used to augment atrophic maxillae in 13 patients. Of the 24 onlay block allografts, 5 were scheduled for vertical alveolar ridge augmentation and the remaining 19 for horizontal alveolar ridge augmentation. Early exposure of the onlay bone graft was observed in 2 patients. All the block grafts showing early exposure had to be completely removed because of infection. All the observed complications were associated with onlay bone grafts placed to increase the vertical dimension of the alveolar ridges. Thirty-eight implants ranging in length from 10 to 15 mm were placed in the area of bone augmentation. All implants inserted achieved satisfactory primary stability. Two implants failed to integrate 6 months after placement during the second stage of surgery. The failed implants were successfully replaced without any need for additional bone grafting. CONCLUSIONS: The use of block allografts to treat maxillary atrophy yielded successful outcomes. Moreover, the augmentation procedure allowed the insertion of implants in the grafted area 5 months after surgery. Therefore, on the basis of this preliminary study, deep-frozen bone allograft can be considered a promising treatment for severe maxillary atrophy, with more extensive follow-up studies being needed to confirm these preliminary data.

Chondrocalcinosis of the temporomandibular joint: clinical considerations and case report.

The calcium pyrophosphate dihydrate crystal deposition disease (CPPD) is a disorder that occasionally affects the temporomandibular joint (TMJ) and is characterized by the presence of crystals in the intra-articular and peri-articular tissues. Diagnosis of CPPD is challenging because clinical symptoms and imaging features are not characteristic and may mimic a chondrosarcoma. A case of a 74-year-old woman with CPPD of the TMJ is reported. This disease rarely involves the TMJ and is not usually considered in the differential diagnosis of temporomandibular disorders (TMD).

Risk of temporomandibular joint effusion related to magnetic resonance imaging signs of disc displacement.

BACKGROUND: It has been suggested that TMJ effusion may represent an inflammatory response to a dysfunctional disc-condyle relationship. The purpose of the present study was to evaluate whether the status of the disc in the temporomandibular joint, as depicted in magnetic resonance (MR) images, is predictive of the presence of temporomandibular joint (TMJ) effusion. METHODS: The relationship between disc displacement and TMJ effusion was analyzed in MR images of 154 TMJs in 77 patients complaining for pain and/or dysfunction in the TMJ area and referred from medical practitioners to specialist consultation. Logistic regression analysis was used to identify the significant correlation between presence/absence of joint effusion and disc displacement. RESULTS: Significant correlation (P<0.01) between disc displacement and joint effusion was found. OR for all type of disc displacement was 3.1, and the odds that a joint had magnetic resonance imaging findings of effusion was greater for anterior disc displacement without reduction. CONCLUSIONS: The status of the disc could represent a factor involved in the development of temporomandibular joint oedema. However, these findings suggest that disc displacement may not be regarded as the dominant factor in defining the occurrence of TMJ effusion. Certain local or systemic conditions other than the disc-condyle relationship must be considered.

Risk of temporomandibular joint effusion related to magnetic resonance imaging signs of disc displacement

Background: It has been suggested that TMJ effusion may represent an inflammatory response to a dysfunctional disc-condyle relationship. The purpose of the present study was to evaluate whether the status of the disc in the temporomandibular joint, as depicted in magnetic resonance (MR) images, is predictive of the presence of temporomandibular joint (TMJ) effusion. Methods: The relationship between disc displacement and TMJ effusion was analyzed in MR images of 154 TMJs in 77 patients complaining for pain and/or dysfunction in the TMJ area and referred from medical practitioners to specialist consultation. Logistic regression analysis was used to identify the significant correlation between presence/absence of joint effusion and disc displacement. Results: Significant correlation (P<0.01) between disc displacement and joint effusion was found. OR for all type of disc displacement was 3.1, and the odds that a joint had magnetic resonance imaging findings of effusion was greater for anterior disc displacement without reduction.Conclusions: The status of the disc could represent a factor involved in the development of temporomandibular joint oedema. However, these findings suggest that disc displacement may not be regarded as the dominant factor in defining the occurrence of TMJ effusion. Certain local or systemic conditions other than the disc-condyle relationship must be considered (AU)

Evaluation of the effectiveness of biobehavioral therapy in the treatment of temporomandibular disorders: a literature review.

Temporomandibular disorders (TMDs) involve a heterogeneous group of clinical conditions affecting the stomatognathic system and its related structures. Because the etiology of these disorders is still unclear, a wide range of therapeutic solutions has been proposed in the literature, including occlusal appliances, physical therapies, drugs, and biobehavioral modalities. Biobehavioral therapy could have a beneficial effect in the treatment of TMDs because of the reportedly high prevalence of psychological dysfunction in TMD patients. The authors reviewed the biobehavioral modalities used to achieve pain relief in patients affected by such disorders, with the aim of synthesizing data on the effectiveness these therapeutic approaches. Literature data suggest that the inclusion of biobehavioral interventions in the management of TMDs may be reasonable, even if no conclusions can be drawn about their long-term effectiveness.