Comparison of Primary Stability of Tapered and Parallel Walled Implants in Poor Quality Bone: An in vitro study

ABSTRACT Objectives: Obtaining primary stability upon placement is crucial for predictable healing and long-term success of dental implants. Primary stability is very difficult and challenging to achieve in poorer quality bone. Currently, two of the more common dental implant designs are tapered and parallel walled dental implants. The objective of this study was to determine if there was a difference in the primary stability of tapered and parallel dental implants in poor quality bone. The null hypothesis of this study was that there is no difference in the primary stability of tapered and parallel walled dental implants in poor quality bone. Material and Methods: Two implant designs (tapered and parallel walled dental implants) were evaluated for the primary stability in a medium that represented poor bone quality (Balsa wood). Twenty-four 4.3 x 11.5 mm HahnTM tapered implants (Glidewell Dental Laboratories, Newport Beach, CA) along with a twenty-four 4.3 mm x 11.5 mm parallel walled prototype HahnTM implants (Glidewell Dental Laboratories, Newport Beach, CA) were used. All implants had identical surface texture, diameter, length, thread design, and pitch thereby eliminating extraneous variables. The only difference between the two dental implants was the taper. After implant placement in the poor quality bone medium, resonance frequency analysis was recorded for each implant using the Penguin RFA (Aseptico®, Woodinville, WA). The ISQ scores were uploaded into Stata 16 (StataCorp, College Station, TX) and evaluated. A two-sample t-test was calculated to determine if there was a statistically significant difference in the primary stability between the two implant designs. Results: In the evaluation of 24 tapered and 24 parallel walled implants, the average ISQ value for the tapered was 67.125 +/- 1.974 and the parallel walled was 64.813 +/- 0.93. The 2-sample ttest yielded a p-value = 0.0000. Since the p-value <0.05, there was a statistically significant difference between the ISQ scores of the two implant designs. The null hypothesis was rejected. Conclusion: The results of this in vitro study concluded that the tapered implant design provides greater primary stability than parallel walled implants in poor quality bone

Large-Scale simulations of plastic neural networks on neuromorphic hardware

SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models

Directed adenovirus evolution using engineered mutator viral polymerases

Adenoviruses (Ads) are the most frequently used viruses for oncolytic and gene therapy purposes. Most Ad-based vectors have been generated through rational design. Although this led to significant vector improvements, it is often hampered by an insufficient understanding of Ad’s intricate functions and interactions. Here, to evade this issue, we adopted a novel, mutator Ad polymerase-based, ‘accelerated-evolution’ approach that can serve as general method to generate or optimize adenoviral vectors. First, we site specifically substituted Ad polymerase residues located in either the nucleotide binding pocket or the exonuclease domain. This yielded several polymerase mutants that, while fully supportive of viral replication, increased Ad’s intrinsic mutation rate. Mutator activities of these mutants were revealed by performing deep sequencing on pools of replicated viruses. The strongest identified mutators carried replacements of residues implicated in ssDNA binding at the exonuclease active site. Next, we exploited these mutators to generate the genetic diversity required for directed Ad evolution. Using this new forward genetics approach, we isolated viral mutants with improved cytolytic activity. These mutants revealed a common mutation in a splice acceptor site preceding the gene for the adenovirus death protein (ADP). Accordingly, the isolated viruses showed high and untimely expression of ADP, correlating with a severe deregulation of E3 transcript splicing

The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin

Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses

Internal Colony--Are You Sure? Defining, Theorizing, Organizing Appalachia

Despite its critics, the internal colony framework has shown remarkable resilience over the years. Successive generations of activists and scholars have targeted “outside interests” as the chief culprits in regional impoverishment, exploitation, and stereotyping. The concentration of land, for example, in the hands of those who reside outside the region seems by definition to represent a form of dispossession that must account for the poverty of many who live here. But is the fact that owners (of land, capital, major media outlets, etc.) are typically not from Appalachia the decisive factor that explains regional degradation? As the need for major economic transitions within Appalachia, perhaps especially the coalfields, becomes more widely accepted, questions about how to define and theorize the past in order to overcome its legacies and organize towards brighter futures become more urgent. Does “internal colony” adequately clarify the context and aims of our struggle? Is ridding the region of outsider ownership and control our central organizing goal? If not, what is? This roundtable explores such questions in the hope of contributing to insights about Appalachia’s past as well as its future

Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+) demonstrated delayed early healing (days 1–3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet), improved wound healing was seen at late time points (days 6–7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds

SIRT3 Regulates Macrophage-Mediated Inflammation in Diabetic Wound Repair

Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds