T lymphocyte development in the absence of Fcϵ receptor Iγ subunit: analysis of thymic-dependent and independent αβ and γδ pathways

During fetal development, early thymocyte progenitors transiently express low affinity Fc receptors for IgG (FcγR) of both FcγRII and III isoforms. Only the FcγRIII isoform requires association of an FcγRIII (CD16) α subunit with an FcϵRIγ homodimer for surface expression. To address the role of FcγR in ontogeny, we studied thymic development in FcϵRIγ^−/− mice. We find that day 14.5 CD4⁻CD8⁻ double-negative (DN) fetal thymocytes of FcϵRIγ^−/− mice express mRNA of both FcγRIIb₁ and FcγRIII. Surface expression of FcγRII/III is readily detected on these cells. It appears that FcγRIIb₁, whose surface expression is FcϵRIγ independent, replaces FcγRIII during thymic development in these animals. Moreover, subsequent development into CD4⁺CD8⁺ double-positive and CD4⁺CD8⁻ and CD4⁻CD8⁺ single-positive subsets appears normal even in the absence of FcϵRIγ. However, alterations were noted in adult animals among the DN αβ TCR⁺ thymocytes and peripheral splenic DN T cells as well as CD8αα⁺ intestinal intraepithelial lymphocytes (iIEL). In contrast to conventional T lymphocytes, which do not express either FcγRIII or FcϵRIγ, DN αβ TCR⁺ thymocytes and extrathymically derived αβ TCR⁺ and γδ TCR⁺ CD8αα⁺β⁻ iIEL express TCR which incorporate FcϵRIγ as one of their subunits. Consistent with this, the TCR levels of these cells are lower than the TCR levels on cells from wild-type C57BL/6 mice. Despite the reduction in the level of surface TCR, the development of these cells was unaltered by the absence of FcϵRIγ. Thus, we observed alterations in adult DN αβ TCR⁺ thymocytes, splenic DN αβ TCR⁺ and DN γδ TCR⁺ large granular lymphocytes (LGL), and αβ TCR⁺ and γδ TCR⁺ CD8αα⁺β⁻ iIEL, but no detectable changes in their major fetal thymic developmental pathways. Cultivation of peripheral DN αβ TCR⁺ and DN γδ TCR⁺ cells from FcϵRIγ^−/− mice with interleukin-2 generates LGL which mediate natural killer activity. Unlike LGL from wild-type C57BL/6 mice, LGL from FcϵRIγ^−/− mice lack FcγRIII expression and could not mediate antibody-dependent cellular cytotoxicity through FcγRIII.     

Homocysteine as a biomarker for cognitive dysfunction in the elderly

PURPOSE OF REVIEW: Homocysteine and B vitamins have been investigated in association with cognitive dysfunction in healthy and in multimorbid elderly patients. Whether reduction of hyperhomocystemia is reducing the risk of dementia or Alzheimer's disease is still under investigation. RECENT FINDINGS: High homocysteine concentrations are associated with poorer cognitive function but can be influenced by a number of factors. The results of epidemiological studies are inconsistent in showing an association between elevated homocysteine levels and dementia or Alzheimer disease. Although prospective studies show a trend towards a benefit of homocysteine-related B vitamin substitution, consistent data are expected from upcoming clinical intervention trials. Data from recent clinical randomized trials including various cognitive tests, different aging groups and supplements in different doses are not sufficient to allow recommendation of homocysteine-reducing therapy with folate or vitamin B12 substitution. According to the published data it remains to be proven whether a reduction in homocysteine will improve cognitive performance. SUMMARY: Homocysteine by itself is not a useful marker for screening cognitive decline, or Alzheimer disease but works as a surrogate parameter for malnutrition and organ insufficiency in the cognitive-declining patient.     

In Vitro Time Efficiency,Fit, and Wear of Conventionally- versus Digitally-Fabricated Occlusal Splints

The purpose of the study was to compare conventional to digital workflows of occlusal splint production regarding time efficiency, overall fit, and wear. Fifteen Michigan splints were fabricated with a conventional and digital method. The duration for the dentist’s and the dental technician’s workload was recorded. Subsequently, the overall fit was examined with a four-level score (1–4). Paired t-tests were used to compare the time results for the conventional and digital workflows and the sign test to compare the overall fit. The mean time (16 min 58 s) for computerized optical impressions was longer than for conventional impressions (6 min 59 s; p = 0.0001). However, the dental technician needed significantly less mean time for the digital splint production (47 min 52 s) than for the conventional (163 min 32 s; p = 0.001). The overall fit of the digitally-fabricated splints was significantly better compared to the conventionally-fabricated splints (p = 0.002). There was no impact of the different materials used in the conventional and digital workflow on the wear (p = 0.26). The results suggest that the digital workflow for the production of occlusal splints is more time efficient and leads to a better fit than the conventional workflow.     

A Novel Zirconia-Based Composite Presents an Aging Resistant Material for Narrow-Diameter Ceramic Implants

A novel ceria-stabilized zirconia-alumina-aluminate composite (Ce-TZP-comp) that is not prone to aging presents a potential alternative to yttrium-stabilized zirconia for ceramic oral implants. The objective of this study was to evaluate the long-term stability of a one-piece narrow-diameter implant made of Ce-TZP-comp. Implant prototypes with a narrow (3.4 mm) and regular (4.0 mm) diameter were embedded according to ISO 14801, and subgroups (n = 8) were subsequently exposed to dynamic loading (10⁷ cycles, 98N) and/or hydrothermal treatment (aging, 85 °C). Loading/aging was only applied as a combined protocol for the 4.0 mm diameter implants. One subgroup of each diameter remained untreated. One sample was cross-sectioned from each subgroup and evaluated with a scanning electron microscope for phase-transformation of the lattice. Finally, the remaining samples were loaded to fracture. A multivariate linear regression model was applied for statistical analyses (significance at p < 0.05). All samples withstood the different loading/aging protocols and no transformation propagation was observed. The narrow diameter implants showed the lowest fracture load after combined loading/aging (628 ± 56 N; p < 0.01), whereas all other subgroups exhibited no significantly reduced fracture resistance (between 762 ± 62 and 806 ± 73 N; p > 0.05). Therefore, fracture load values of Ce-TZP-comp implants suggest a reliable intraoral clinical application in the anterior jaw regions.     

One‐piece zirconia oral implants for single‐tooth replacement: Three‐year results from a long‐term prospective cohort study

Aim

This 3‐year report of a prospective long‐term cohort investigation aimed to evaluate the clinical and radiographic outcomes of a one‐piece zirconia oral implant for single‐tooth replacement.

Materials and Methods

Sixty‐five patients received a 1‐stage implant surgery with immediate temporization. Standardized radiographs were taken at implant insertion, after 1 year, and after 3 years to monitor peri‐implant bone levels. A univariate analysis of the association of different baseline parameters on marginal bone loss from implant insertion to 36 months was performed. Soft‐tissue parameters were evaluated at prosthesis insertion, after 6 months, after 1 year, and at the 3‐year follow‐up.

Results

After 3 years, six posterior site implants were lost, giving a cumulative survival rate of 90.8%. The mean marginal bone loss was 1.45 mm; 35% of the implants lost at least 2 mm bone, and 22% more than 3 mm. The univariate analysis did not identify any parameter associated with marginal bone loss. Probing depth, clinical attachment level, and bleeding index increased over 3 years, and plaque index decreased.

Conclusions

The low survival rate of the presented ceramic implant and especially the high frequency of advanced bone loss are noticeable but remain unexplained.     

Initial Bacterial Adhesion on Different Yttria-Stabilized Tetragonal Zirconia Implant Surfaces in Vitro

Bacterial adhesion to implant biomaterials constitutes a virulence factor leading to biofilm formation, infection and treatment failure. The aim of this study was to examine the initial bacterial adhesion on different implant materials in vitro. Four implant biomaterials were incubated with Enterococcus faecalis, Staphylococcus aureus and Candida albicans for 2 h: 3 mol % yttria-stabilized tetragonal zirconia polycrystal surface (B1a), B1a with zirconium oxide (ZrO₂) coating (B2a), B1a with zirconia-based composite coating (B1b) and B1a with zirconia-based composite and ZrO₂ coatings (B2b). Bovine enamel slabs (BES) served as control. The adherent microorganisms were quantified and visualized using scanning electron microscopy (SEM); DAPI and live/dead staining. The lowest bacterial count of E. faecalis was detected on BES and the highest on B1a. The fewest vital C. albicans strains (42.22%) were detected on B2a surfaces, while most E. faecalis and S. aureus strains (approximately 80%) were vital overall. Compared to BES; coated and uncoated zirconia substrata exhibited no anti-adhesive properties. Further improvement of the material surface characteristics is essential.     

Prevalence of anemia among elderly inpatients and its association with multidimensional loss of function

The purpose of this cross-sectional prospective study was to determine the prevalence of anemia among elderly hospitalized patients in Germany and to investigate its association with multidimensional loss of function (MLF). One hundred participants aged 70 years or older from two distinct wards (50 each from an emergency department and a medical ward, respectively) underwent a comprehensive geriatric assessment (CGA) consisting of the following six tools: Barthel Index, mini-mental state examination, clock-drawing test, timed up and go test, Esslinger transfer scale, and Daniels test. MLF as an aggregated outcome was diagnosed when three or more tests of the CGA showed an abnormal result. Anemia was defined according to WHO criteria as a hemoglobin (Hb) concentration of <13 g/dL for men and <12 g/dL for women. The prevalence of anemia was 60 %. Overall, 61 % of patients presented with three or more abnormal results in the six tests of the CGA and, thus, with MLF. Using logistic regression, we found a significant association of both anemia and low Hb concentrations with abnormal outcomes in five tests of the CGA and, therefore, with domain-specific deficits like mobility limitations, impaired cognition, and dysphagia. Furthermore, being anemic increased the odds of featuring MLF more than fourfold. This significant relationship persisted after adjustment for various major comorbidities. Both anemia and geriatric conditions are common in the hospitalized elderly. Given the association of anemia with MLF, Hb level might serve as a useful geriatric screening marker to identify frail older people at risk for adverse outcomes.     

Differences in morphogenesis of 3D cultured primary human osteoblasts under static and microfluidic growth conditions

As information on osteoblast mechanosensitivity response to biomechanical cues in three-dimensional (3D) in vitro microenvironments is sparse, the present study compared morphogenesis of primary human alveolar bone osteoblasts (PHABO) under microchip-based 3D-static conditions, and 3D-fluid flow-mediated biomechanical stimulation in perfusion bioreactors. Discrimination of the respective microenvironment by differential morphogenesis was evident from fluid flow-induced PHABO reorganization into rotund bony microtissue, comprising more densely packed multicellular 3D-aggregates, while viability of microtissues was flow rate dependent. Time-lapse microscopy and simple modeling of biomechanical conditions revealed that physiologically relevant fluid flow-mediated PHABO stimulation was associated with formation of mulberry-like PHABO aggregates within the first 24 h. Differential extracellular matrix deposition patterns and gene expression modulation in PHABO aggregates at day 7 further indicates progressive osteoblast differentiation exclusively in perfusion culture-developed bony microtissues. The results of our study strongly suggest PHABO morphogenesis as discriminator of microenvironmental growth conditions, which in case of the microfluidic 3D microchip-bioreactor are substantiated by triggering in vitro bone microtissue formation concomitant with progressive osteoblastic differentiation. Such microtissue outcomes provide unique insight for mechanobiological studies in response to biomechanical fluid flow cues, and clinically appear promising for in vitro PHABO preconditioning, enabling innovative bone augmentation procedures.