A complete digital approach for facially generated full arch diagnostic wax up, guided surgery, and implant-supported interim prosthesis by integrating 3D facial scanning, intraoral scan and CBCT.

Continuous innovation in digital dental technology offers new prospects for creating a complete virtual environment. The technique described adds a facial approach to the conventional digital workflow by incorporating 3D face scans to cone beam computed tomography and intraoral scans. Using this workflow, clinicians can obtain a complete virtual patient for facially generated diagnostic wax up and plan and implement a predictable implant placement and interim prosthesis. This technique provides a full digital workflow for restoratively-driven computer-aided implant planning, guided surgery, and 3D printing of an interim complete-arch fixed implant-supported prosthesis.

Impact of breath-hold technique on incidence of cardiac events in adjuvant left breast cancer irradiation.

BACKGROUND: This study aims to compare the incidence of cardiac events and to identify its predictors in left breast cancer patients receiving adjuvant radiotherapy using breath-hold technique (DIBH) versus free breathing technique (FB). METHODS: We conducted a retrospective multi-center study of two arms; the free breathing arm included 208 patients who were treated with traditional radiotherapy treatment technique, while DIBH arm included 224 patients who were treated with breath-hold technique using The Varian Real-time Position Management (RPM). We retrospectively reviewed the medical records of the patients from January 2010 to December 2017. RESULTS: The mean dose to the heart and left anterior descending artery were significantly lower in the DIBH arm (2.10 ± 0.39 and 6.16 ± 0.18 Gy) compared with (4.29 ± 0.60 Gy and 12.69 ± 0.93 Gy, respectively) in the FB arm. The incidence of cardiac events was higher in the FB arm than in the DIBH arm, but it was not statically significant. Our analysis revealed that age, diabetes, hypertension, smoking, mean LAD dose, and heart mean dose were significant prognostic factors for the occurrence of cardiac events in the breath-hold arm. Hypertension, smoking, as well as heart mean dose were independent risk factors for the occurrence of cardiac events. CONCLUSION: Use of the DIBH technique resulted in a significant reduction in doses to the heart, LAD and lesser cardiac events incidence compared to free breathing.

Evaluating the accuracy of intraoral direct digital impressions in 2 infants with unilateral cleft lip and palate compared with digitized conventional impression.

INTRODUCTION: Presurgical infant orthopedics was introduced as an interceptive approach for treating cleft lip and/or palate (CLP). This study aimed to evaluate the intraoral digital impression technique as a viable alternative to conventional impression in infants with unilateral CLP. METHODS: Trios 3-Shape scanner (3Shape, Copenhagen, Denmark) was used for intraoral scanning of the infants' maxillary arches to provide a direct digital scan (DDS). In addition, conventional impressions of the same patients were taken in a hospital setting, and the resultant stone models were digitized using the same scanner to create an indirect digital scan (IDS). Both scans (DDS and IDS) were exported in stereolithography format, and the resultant stereolithography files were imported into computer-assisted-design software (Exocad DentalCAD; exocad GmbH, Darmstadt, Germany) for 3-dimensional surface model superimposition. Differences between the 2 surfaces were quantified in millimeters and visually displayed by a color map. RESULTS: Three-dimensional surface model superimposition of the DDS and IDS scans showed an excellent agreement between both approaches, in which differences ranged from 0.01 mm to 0.1 mm CONCLUSIONS: Intraoral direct digital impression in infants with unilateral CLP is a safe, accurate, and time-efficient technique, which can be a viable alternative to conventional impression. This will aid in overcoming the challenges and complications that are frequently associated with using conventional impressions in infants with unilateral CLP, thus reducing the burden of care not only on the patients' families but also on the care providers.

Analysis of metabolic network disruption in engineered microbial hosts due to enzyme promiscuity.

Increasing understanding of metabolic and regulatory networks underlying microbial physiology has enabled creation of progressively more complex synthetic biological systems for biochemical, biomedical, agricultural, and environmental applications. However, despite best efforts, confounding phenotypes still emerge from unforeseen interplay between biological parts, and the design of robust and modular biological systems remains elusive. Such interactions are difficult to predict when designing synthetic systems and may manifest during experimental testing as inefficiencies that need to be overcome. Transforming organisms such as Escherichia coli into microbial factories is achieved via several engineering strategies, used individually or in combination, with the goal of maximizing the production of chosen target compounds. One technique relies on suppressing or overexpressing selected genes; another involves introducing heterologous enzymes into a microbial host. These modifications steer mass flux towards the set of desired metabolites but may create unexpected interactions. In this work, we develop a computational method, termed Metabolic Disruption Workflow (MDFlow), for discovering interactions and network disruptions arising from enzyme promiscuity - the ability of enzymes to act on a wide range of molecules that are structurally similar to their native substrates. We apply MDFlow to two experimentally verified cases where strains with essential genes knocked out are rescued by interactions resulting from overexpression of one or more other genes. We demonstrate how enzyme promiscuity may aid cells in adapting to disruptions of essential metabolic functions. We then apply MDFlow to predict and evaluate a number of putative promiscuous reactions that can interfere with two heterologous pathways designed for 3-hydroxypropionic acid (3-HP) production. Using MDFlow, we can identify putative enzyme promiscuity and the subsequent formation of unintended and undesirable byproducts that are not only disruptive to the host metabolism but also to the intended end-objective of high biosynthetic productivity and yield. As we demonstrate, MDFlow provides an innovative workflow to systematically identify incompatibilities between the native metabolism of the host and its engineered modifications due to enzyme promiscuity.

Incidence of Pre-Existing Lingual Cortex Perforation Before Removal of Mandibular Third Molars.

PURPOSE: The objective of this study was to determine the relationship between the mandibular third molar tooth (Md3) and the adjacent lingual cortical bone and determine the incidence of lingual cortex perforation by Md3s. PATIENTS AND METHODS: This retrospective study was designed and implemented from 100 cone-beam computed tomographic scans (CBCTs) of patients with age ranging from 18 to 65 years old. The primary outcome was to assess the incidence of mandibular third molars (Md3s) with existing lingual cortex perforation by their roots. Perforation was assessed at the level of root apex and the most lingual portion on the apical half of the root. Other outcome variables included average thickness of covering lingual bone in the nonperforation group, lingual cortex morphology, impaction, and demographics. Descriptive statistics were computed. RESULTS: More than half the radiographs showed lingual cortex perforation at the level of root apex and most lingual portion on the apical one half of the root (51.2% and 52.8%, respectively). The average thickness of the covering lingual bone was 1.25 mm around the root apex and 0.93 mm around the most lingual portion on the apical half of the root. The most common lingual cortex morphology was the undercut shape. There was statistically significant association between the presence of Md3 impaction and perforation at both root levels [(P value < .001, Effect size = 0.378) and (P value < .001, Effect size = 0.445)]. CONCLUSIONS: Perforation of the lingual cortex by Md3s, whether erupted or impacted, was found in >50% of patients as determined by a preoperative CBCT scan. Therefore, the finding of lingual cortex perforation after removal of Md3s is likely to be evidence of a pre-existing condition rather than a result of surgery.

Towards creating an extended metabolic model (EMM) for E. coli using enzyme promiscuity prediction and metabolomics data.

BACKGROUND: Metabolic models are indispensable in guiding cellular engineering and in advancing our understanding of systems biology. As not all enzymatic activities are fully known and/or annotated, metabolic models remain incomplete, resulting in suboptimal computational analysis and leading to unexpected experimental results. We posit that one major source of unaccounted metabolism is promiscuous enzymatic activity. It is now well-accepted that most, if not all, enzymes are promiscuous-i.e., they transform substrates other than their primary substrate. However, there have been no systematic analyses of genome-scale metabolic models to predict putative reactions and/or metabolites that arise from enzyme promiscuity. RESULTS: Our workflow utilizes PROXIMAL-a tool that uses reactant-product transformation patterns from the KEGG database-to predict putative structural modifications due to promiscuous enzymes. Using iML1515 as a model system, we first utilized a computational workflow, referred to as Extended Metabolite Model Annotation (EMMA), to predict promiscuous reactions catalyzed, and metabolites produced, by natively encoded enzymes in Escherichia coli. We predict hundreds of new metabolites that can be used to augment iML1515. We then validated our method by comparing predicted metabolites with the Escherichia coli Metabolome Database (ECMDB). CONCLUSIONS: We utilized EMMA to augment the iML1515 metabolic model to more fully reflect cellular metabolic activity. This workflow uses enzyme promiscuity as basis to predict hundreds of reactions and metabolites that may exist in E. coli but may have not been documented in iML1515 or other databases. We provide detailed analysis of 23 predicted reactions and 16 associated metabolites. Interestingly, nine of these metabolites, which are in ECMDB, have not previously been documented in any other E. coli databases. Four of the predicted reactions provide putative transformations parallel to those already in iML1515. We suggest adding predicted metabolites and reactions to iML1515 to create an extended metabolic model (EMM) for E. coli.

Establishing synthesis pathway-host compatibility via enzyme solubility.

Current pathway synthesis tools identify possible pathways that can be added to a host to produce the desired target molecule through the exploration of abstract metabolic and reaction network space. However, not many of these tools explore gene-level information required to physically realize the identified synthesis pathways, and none explore enzyme-host compatibility. Developing tools that address this disconnect between abstract reactions/metabolic design space and physical genetic sequence design space will enable expedited experimental efforts that avoid exploring unprofitable synthesis pathways. This work describes a workflow, termed Probabilistic Pathway Assembly with Solubility Confidence Scores (ProPASS), which links synthesis pathway construction with the exploration of the physical design space as imposed by the availability of enzymes with predicted characterized activities within the host. Predicted protein solubility propensity scores are used as a confidence level to quantify the compatibility of each pathway enzyme with the host Escherichia coli (E. coli). This study also presents a database, termed Protein Solubility Database (ProSol DB), which provides solubility confidence scores in E. coli for 240,016 characterized enzymes obtained from UniProtKB/Swiss-Prot. The utility of ProPASS is demonstrated by generating genetic implementations of heterologous synthesis pathways in E. coli that target several commercially useful biomolecules.