The Impact of Technological Innovation on Dentistry.

Technology has revolutionized the way dentists are able to treat their patients. These technological advances have paved the way for the creation of virtual patient models utilizing these 3-dimensional intra-oral patient models, cone bean computer tomography (CBCT) radiograph scans, extraoral 3-dimensional scans, and jaw motion tracings to create a patient-specific model. These models are advantageous in planning surgical treatments by providing 3-dimensional views of vital anatomical structures to accurately identify the location, size, and shape of a structure or defect in order to plan accordingly. Virtual augmentation of either hard tissue (bone) and/or soft tissue (i.e., gingiva) can also be accomplished.Technology has allowed the capture of the dynamic motions of the jaw and combined them with the virtual patient to develop permanent restorations in harmony with the patient's orofacial complex. With the introduction of new technology in the realm of digital dentistry, patient care is being brought to a new and higher level. This creates a level of more optimal care that a dentist can deliver to patients.

CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer.

BACKGROUND: Response to immune checkpoint blockade (ICB) in ovarian cancer remains disappointing. Several studies have identified the chemokine CXCL9 as a robust prognosticator of improved survival in ovarian cancer and a characteristic of the immunoreactive subtype, which predicts ICB response. However, the function of CXCL9 in ovarian cancer has been poorly studied. METHODS: Impact of Cxcl9 overexpression in the murine ID8-Trp53-/- and ID8-Trp53-/-Brca2-/- ovarian cancer models on survival, cellular immune composition, PD-L1 expression and anti-PD-L1 therapy. CXCL9 expression analysis in ovarian cancer subtypes and correlation to reported ICB response. RESULTS: CXCL9 overexpression resulted in T-cell accumulation, delayed ascites formation and improved survival, which was dependent on adaptive immune function. In the ICB-resistant mouse model, the chemokine was sufficient to enable a successful anti-PD-L1 therapy. In contrast, these effects were abrogated in Brca2-deficient tumours, most likely due to an already high intrinsic chemokine expression. Finally, in ovarian cancer patients, the clear-cell subtype, known to respond best to ICB, displayed a significantly higher proportion of CXCL9high tumours than the other subtypes. CONCLUSIONS: CXCL9 is a driver of successful ICB in preclinical ovarian cancer. Besides being a feasible predictive biomarker, CXCL9-inducing agents thus represent attractive combination partners to improve ICB in this cancer entity.

Gender differences in examination behavior of 4th grade medical students : Results from an observational study on ECG e-learning.

BACKGROUND: Computer-assisted teaching is becoming increasingly more important to acquire new knowledge and skills in medical curricula. The consequence of gender-characteristic personality traits on academic performance in e­learning examinations are difficult to forecast. This study investigated gender-related differences in examination behavior among undergraduate medical students taking a web-based quiz. METHODS: A total of 1315 4th grade medical students at the Medical University of Vienna completing the compulsory online moodle-based ECG quiz 2017/2018 were enrolled into this observational study. Individual data of examination behavior and quiz results as well as results of the final annual exam were extracted. Students were grouped into 10 strata according to academic performance. Variables between both sexes were compared using a nonparametrical test. Examination variables were correlated to performance. RESULTS: Of the total study population 686 (52%) were female and 629 (48%) were male. The time until the first attempt and number of attempts performed was comparable between both sexes, however female students spent more time on the first attempt compared to their male colleagues (1592 sec [Q1-Q3: 999-2536] vs 1405 sec [Q1-Q3: 828-2395], p = 0.002), suggesting a higher self-discipline and risk-aversity. There was no difference regarding quiz scores or final ECG examination scores between female and male students (p = 0.869 and p = 0.396). Students who accessed the quiz earlier and less time spent for the first attempt tended to perform better at the final examination (rs = 0.20, p < 0.001 and rs = -0.15, p < 0.001). CONCLUSIONS: Gender-related differences in examination behavior already described for nononline based examinations are similarly observable in e­learning. For this test, gender-immanent traits seem not to twist final examination results and impact academic performance.

The Chemokine CX3CL1 Improves Trastuzumab Efficacy in HER2 Low-Expressing Cancer In Vitro and In Vivo.

A crucial mode of action of trastuzumab is the labeling of HER2-positive (HER2+) tumor cells for the eradication by natural killer (NK) cells, a process called antibody-dependent cellular cytotoxicity (ADCC). However, despite widespread HER2 expression among cancer entities, only a fraction, with robust HER2 overexpression, benefits from trastuzumab therapy. ADCC requires both sufficient lymphocytic infiltration and close binding of the immune cells to the antibody-tagged tumor cells. We hypothesized that the chemokine CX3CL1 could improve both processes, as it is synthesized as a membrane-bound, adhesive form that is eventually cleaved into a soluble, chemotactic protein. Here, we show that CX3CL1 overexpression is a positive prognostic marker in breast cancer. CX3CL1 overexpression attracted tumor-suppressive lymphocytes, including NK cells, and inhibited tumor growth and lung metastasis in the syngeneic 4T1 breast cancer mouse model. In HER2+ SKBR3, MDA-MB-453, and HT-29 tumor cells, CX3CL1 overexpression increased NK cell-mediated cytotoxicity in vitro and acted synergistically with trastuzumab. Even though CX3CL1 did not further improve trastuzumab efficacy in vivo in the trastuzumab-sensitive MDA-MB-453 model, it compensated for NK-cell depletion and prolonged survival. In the HER2 low-expressing HT-29 model, however, CX3CL1 overexpression not only prolonged survival time but also overcame trastuzumab resistance in a partly NK cell-dependent manner. Taken together, these findings identify CX3CL1 as a feasible pharmacologic target to enable trastuzumab therapy in HER2 low-expressing cancers and render it a potential predictive biomarker to determine therapy responders.

Case Report of a Program to Enhance Dental Students' Interest in Academic Dentistry.

This case report describes a Teaching Honors Program (THP) at the UT Health San Antonio School of Dentistry and presents findings from an outcomes assessment covering the initial 11 years of the program. The program goals are to enhance dental students' awareness of academic career options, promote student and faculty collaboration on educational development projects, and provide students with training in teacher toolkit skills to increase their readiness for peer teaching during dental school and faculty roles early in their careers. The THP curriculum consists of six core courses and nine electives extending across the four years of dental school. THP graduates receive the academic designation "Distinction in Dental Education" at commencement. Outcomes data are organized by Kirkpatrick's Hierarchy of Educational Outcomes: reaction (participants' satisfaction with THP), indicators (students' attitudes and intentions pertinent to teaching and academic careers), learning (changes in knowledge and skills relevant to teachers' tasks), behavior (students' ability to apply teaching skills in classrooms, labs, and clinics), and results (changes in the infrastructure and capacity of the school as a consequence of the THP). Positive outcomes were found in multiple layers of the assessment hierarchy. In 2016, 51% of students participated in the THP, and 31 graduated with Distinction in Dental Education; in 2017, 50% participated, and 44 graduated with that honor. THP students provide approximately 1,400 hours of supervised peer teaching annually in the predoctoral curriculum and pre-matriculation programs, and 21% of the initial 106 THP graduates entered academic dentistry soon after graduation.

PI3K: A master regulator of brain metastasis-promoting macrophages/microglia.

Mutations and activation of the PI3K signaling pathway in breast cancer cells have been linked to brain metastases. However, here we describe that in some breast cancer brain metastases samples the protein expression of PI3K signaling components is restricted to the metastatic microenvironment. In contrast to the therapeutic effects of PI3K inhibition on the breast cancer cells, the reaction of the brain microenvironment is less understood. Therefore we aimed to quantify the PI3K pathway activity in breast cancer brain metastasis and investigate the effects of PI3K inhibition on the central nervous system (CNS) microenvironment. First, to systematically quantify the PI3K pathway activity in breast cancer brain metastases, we performed a prospective biomarker study using a reverse phase protein array (RPPA). The majority, namely 30 out of 48 (62.5%) brain metastatic tissues examined, revealed high PI3K signaling activity that was associated with a median overall survival (OS) of 9.41 months, while that of patients, whose brain metastases showed only moderate or low PI3K activity, amounted to only 1.93 and 6.71 months, respectively. Second, we identified PI3K as a master regulator of metastasis-promoting macrophages/microglia during CNS colonization; and treatment with buparlisib (BKM120), a pan-PI3K Class I inhibitor with a good blood-brain-barrier penetrance, reduced their metastasis-promoting features. In conclusion, PI3K signaling is active in the majority of breast cancer brain metastases. Since PI3K inhibition does not only affect the metastatic cells but also re-educates the metastasis-promoting macrophages/microglia, PI3K inhibition may hold considerable promise in the treatment of brain metastasis and the respective microenvironment.

Allergies and autoimmune disorders in children after heart transplantation.

Pediatric heart transplantation requires lifelong immune suppression and may require thymectomy, both of which alter T-cell repertoires. We hypothesized that atopic and autoimmune diseases are more common in pediatric heart transplant patients than the general population, and that transplantation in early childhood increases the risk of development or worsening of atopic or autoimmune disease. A cross-sectional single-center study including 21 heart transplant patients aged ≤18 years was conducted. Data collected included age at transplant, induction, thymectomy, and development and severity of atopic or autoimmune disease. A majority (67%) reported having any atopic disease post-transplant, all of whom reported onset or worsening post-transplantation. Thymectomized patients were significantly more likely to have asthma (P = 0.018) and report asthma worsening post-transplant (P = 0.045). Patients with worsening of asthma post-transplant were transplanted at a significantly younger age (P = 0.040). ABO incompatible and ABO compatible recipients presented similarly. Anemia was common (38%) but not always clearly of autoimmune origin. Atopic diseases are common in children following heart transplantation: Compared to the general population, there is a higher prevalence of eczema (43% vs 11%) and asthma (33% vs 9%). Both thymectomy and younger age at transplant are associated with atopic disorders, possibly due to altered T-cell repertoires.

Management of anaphylaxis and allergies in patients with long QT syndrome: A review of the current evidence.

OBJECTIVE: To develop a treatment algorithm for patients with long QT syndrome (LQTS) in case they need antiallergic medications for allergic reactions, including asthma and anaphylaxis. DATA SOURCES: A literature review was performed to assess safety and to develop antiallergic treatment strategies for patients with LQTS. STUDY SELECTIONS: LQTS is a heterogeneous group of myocardial repolarization disorders characterized by prolongation of the QT interval that potentially results in life-threatening torsades de pointes tachycardia. Data on pharmacologic treatment in case of anaphylaxis in LQTS are sparse. For this narrative review, all currently available articles on the use of antiallergic drugs for allergic reactions, anaphylaxis, and asthma in patients with LQTS were used. RESULTS: Local allergic symptoms can be safely treated primarily with fexofenadine, levocetirizine, desloratadine, or cetirizine and, if needed, a short course of corticosteroids. In case of systemic symptoms, epinephrine should be administered. It may be less effective in patients with LQTS treated with ß-blockers, necessitating the use of glucagon as add-on treatment. In case of lower airway obstruction, ipratropium bromide should be used, but if not effective, inhaled ß2-adrenergic agents may be used. Continuous cardiac monitoring is indicated with the use of epinephrine and inhaled ß2-adrenergic agents. The use of the latter also warrants intense monitoring of serum potassium levels. Clemastine and dimetindene should be avoided in patients with LQTS. CONCLUSION: Patients with LQTS have a higher risk of life-threatening complications during the treatment of their allergic reactions because of the underlying disease and concomitant treatment with ß-blockers. Treatment algorithms will certainly decrease these complications.

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G.

Age-related diseases, such as osteoarthritis, Alzheimer's disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging.

Expansion of a Predoctoral Surgical Implant Selective for Dental Students.

Historically, predoctoral dental education programs have focused on the restoration of implants in the clinical environment; however, given the increase in dental implant therapy being performed by general dentists, the need to incorporate surgical implant training is becoming evident. This article describes a predoctoral surgical implant selective at the University of Texas Health Science Center at San Antonio and its evolution across five years to include emerging techniques and technology to enhance students' understanding of dental implant therapy, both surgical and restorative. From virtual implant planning and guided surgery to intra-oral scanning of implants for custom abutments and restorations, students obtained first-hand experiences with a wide spectrum of aspects of implant therapy. The results of anonymous surveys completed by 2014-15 students before and after the year-long selective regarding their impression of the program are also discussed.

A Combination of Various Technologies in the Fabrication of a Removable Partial Denture--A Case Study.

Digital dentistry is increasing prevalent throughout general dental practice. Scanned impression systems, CAD/CAM software, milling units, and 3D printers are becoming used with regularity by some private practitioners. This case report describes a combination of multiple technologies including intraoral scanning, 3D printing, and traditional impression and processing techniques used for fabricating a removable partial denture. The patient indicated that he was highly satisfied throughout the course of treatment and especially with the final result. Future technology will continue to evolve and be more widely used in removable prosthodontics and other areas of dentistry.

The use of virtual models to estimate the amount of grafting material: a case study.

The authors present a case study in which a virtual model was created from a patient's cone beam computed tomographic scans that simulated a dentoalveolar defect associated with periapical pathosis. With the information provided by the virtual model, the tooth was extracted, and both defect and alveolus were virtually grafted. The virtual amount calculated was similar to the amount used in the actual site.

Digital dentistry and implant dentistry--a case study.

In the area of fixed prosthodontics, implants have evolved to become the gold standard in terms of longevity and esthetic outcome (1). As in all of dentistry, careful diagnosis and treatment planning is a must to achieve an optimum result. When evaluating the recipient site, one must determine if any type of defect (hard or soft tissue) exists which would require augmentation. The existing occlusion must also be evaluated to ensure the dentist is aware of possible prosthetic complications. In straightforward cases, such as those without the need for augmentation, the conventional timeline requires a waiting period of 3 months following surgical placement to begin the restorative procedures. Factoring in the restorative time frame, the patient may wait up to approximately 4 months for the final implant prosthesis. Various advancements in dentistry are changing the way dentists approach implant dentistry--from diagnosis and treatment planning to final restorations. This article illustrates these advances through a case study.

Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.

The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3-30 µM), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3α-acetoxy-8,24-dienetirucallic acid (6) and 3α-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 µM, each. Structure-activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 µM). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids.

Mechanical ventricular assist device as a bridge to recovery post-ABO-incompatible heart transplantation for failed Fontan circulation.

A girl received an ABO-incompatible heart transplantation (ABOiHTx) at the age of 3.5 years for failed univentricular palliation with protein-losing enteropathy (PLE). She was born with a hypoplastic left heart syndrome and underwent multistage palliation to a Fontan circulation at 2½ years of age. After the Fontan surgery, she developed PLE, necessitating a Fontan revision, followed by a Fontan takedown and eventually HTx, which was performed with a blood group B heart into an O recipient. Right ventricular (RV) failure secondary to increased pulmonary vascular resistance (PVR) evolved immediately after HTx. A temporary right ventricular assist device (RVAD) was implanted and later switched to a pneumatic pulsatile RVAD. With the adaption of PVR on the RVAD, the PLE resolved and the RVAD was explanted. In the following 12 months, she developed multiple relapses of PLE which eventually resolved after exchange of the calcineurin inhibitor.

Using CAD/CAM technology to create a 10-unit zirconia fixed partial denture--a UTHSCSA dental school case report.

From diagnosis and treatment planning to the materials being used, technology is changing dentistry. New materials are providing dentists greater options for treatment, while technology is streamlining the workflow in the office and dental laboratory. Traditionally the creation of a long-span fixed partial denture was a labor intense project--from waxing up the prosthesis--to stacking of the porecelain. For larger frameworks, it was recommended for the dentist to bring in the patient in for a framework try-in. However, advances in both CAD/CAM technology and dental materials are revolutionizing the way dentistry is being done. The following describes the fabrication of a 10-unit full contour zirconia fixed partial denture completed in the pre-doctorate program at UTHSCSA Dental School.

CAD/CAM and lithium disilicate: an anterior esthetic case study.

Digital technology has brought a new and exciting dimension to dental esthetics. Innovative ways to take impressions and create chair-side restorations are continuing to expand and new dental materials specifically made for CAD/CAM are allowing for extremely esthetic restorations. Lithium disilicate is one such material that is efficiently milled, has a favorable flexural strength, and provides highly esthetic chair-side restorations. The following is a case study that utilizes lithium disilicate for esthetic full coverage crowns on teeth #7, 8, 9, and 10.