Three-dimensionally printed duplicate sleeping denture.

A patient presented with a treatment plan for the replacement of his maxillary complete removable denture and mandibular implant-retained complete overdenture because of excessive wear and fracture of his existing prostheses. A digital workflow was used, and his dentures were milled from a monolithic acrylic resin disk. Upon delivery of the dentures, the patient reported that he was unable to sleep without his dentures in place although he denied a diagnosis of obstructive sleep apnea. After emphasizing the recommendation to remove his dentures while sleeping, it was decided to use additive manufacturing technology because of its low cost and ability to faithfully reproduce a 3-dimensional file in various biocompatible materials. The second set of sleeping dentures were 3-dimensionally printed and delivered with minimal adjustment and at a low cost.

A combined conventional-digital workflow for predictable cross-arch guide plane reduction.

A combined conventional and digital workflow is described to print a 3-dimensional complete-arch reduction guide. This was used to prepare guide planes with cross-arch parallelism in the distal of both maxillary first molars, the mesial of both maxillary first premolars, and the distolingual of both maxillary central incisors for a patient requiring a removable partial denture to replace missing bilateral maxillary lateral incisors and canines. The 3-dimensionally printed guide was placed on the remaining teeth in the arch and used as both a visual guide and a guide for tooth preparation.

Comparison of the fit of surgical guides manufactured with low-cost 3D printers.

In-office printing of surgical guides is becoming increasingly common in the modern dental practice. This in vitro study sought to evaluate the accuracy of fit of surgical guides printed with 4 low-cost desktop 3-dimensional (3D) printers: SparkMaker Original, Photon, MP Mini SLA, and Epax X1. All of the printers in this study were released after 2017 and purchased for less than $500. All of the 3D printers were capable of printing biocompatible surgical guide resin. To evaluate the accuracy of the printers, a total of 20 surgical guides were produced with the 4 printers (n = 5) from the same stereolithography (STL) file using the same resin. The guides were then scanned with a laboratory scanner, and the intaglio surface was compared to the master STL file using metrology software. The null hypothesis was that, across printers, the intaglio surfaces of the printed surgical guides would achieve the standard of at least 80% of the surface fitting within a 100- µm tolerance level. Data were analyzed with the Tukey-Kramer test (P < 0.05). Three of the 4 printers (SparkMaker Original, Photon, and Epax X1) were able to consistently produce surgical guides within the accepted tolerance values. The Epax X1 surgical guide group had a significantly higher mean percentage of fit within the tolerance level (P < 0.05), indicating that this printer produced the greatest accuracy relative to the original STL file.

Guidelines versus evidence: what we can learn from the Australian guideline for low-level laser therapy in knee osteoarthritis? A narrative review.

This narrative review analyses the Australian Guideline (2018) for the treatment of knee osteoarthritis (KOA) developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The Guideline recommended against the use low-level laser therapy (LLLT). Why this conclusion was reached is discussed in this review in the context of evidence provided in other systematic reviews, the latest of which was published in 2019 and which provided strong support for LLLT for knee OA. We evaluated the reference list cited for the recommendation "against" LLLT and compared this with reference lists of systematic reviews and studies published before and after the publication date of the Guideline. Eight randomised controlled trials (RCTs) of LLLT were cited in the Guideline the latest of which was published in 2012. There were seventeen additional RCTs, five of which together with one systematic review were located in the year of publication, 2018. The most recent systematic review in 2019 included 22 RCTs in its analysis. Discordance with the levels of evidence and recommendations was identified. Although GRADE methodology is said to be robust for systematically evaluating evidence and developing recommendations, many studies were not identified in the Guideline. In contrast, the latest systematic review and meta-analysis provides robust evidence for supporting the use of LLLT in knee OA. The conflict between guidelines based on opinion and evidence based on meta-analysis is highlighted. Given the totality of the evidence, we recommend that the Australian Guideline should be updated immediately to reflect a "for" recommendation.

Risk factors and clinical outcomes associated with fixed airflow obstruction in older adults with asthma.

BACKGROUND: Asthma in older adults is associated with increased morbidity and mortality compared with asthma in younger patients. Fixed airflow obstruction (FAO) is associated with decreased survival in younger patients, but its significance remains unclear in older adults with asthma. OBJECTIVE: To identify risk factors and outcomes related to FAO in older adults with asthma. METHODS: Subjects older than 55 years with a physician diagnosis of persistent asthma were evaluated. Collected data included participant demographic information, medications, asthma exacerbations, Asthma Control Test (ACT) score, Asthma Quality of Life (AQLQ) score, comorbidities, spirometry, atopic status, and fractional exhaled nitric oxide. Clinical characteristics and outcomes associated with FAO (defined as post-bronchodilator ratio of forced expiratory volume in 1 second to forced vital capacity ≤70%) were assessed. RESULTS: A total of 186 participants were analyzed (48 men and 138 women, mean age 66 years). FAO was demonstrated in 30% of participants. Using regression analysis, predictors of FAO included advanced age, African American race, male sex, and longer duration of asthma. In outcomes analysis, FAO was associated with worsened ACT and AQLQ scores; however, after controlling for confounding factors, logistic regression showed no association. No significant association was found between FAO and exacerbations, fractional exhaled nitric oxide, atopy, rhinitis, education level, depression, smoking, or body mass index. CONCLUSION: Risk factors associated with FAO in older adults with asthma include advanced age, African American race, increased asthma duration, and male sex. Unlike younger patients, FAO is not independently associated with worsened asthma control, quality of life, or exacerbations in older patients with asthma. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01979055.

Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.

Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc.

Hereditary angioedema with a focus on the child.

Hereditary angioedema (HAE) is a rare disease that causes recurrent mucosal and cutaneous swelling. Skin swelling, abdominal pain, and airway swelling cause significant morbidity and potential mortality. Symptoms often appear early in life and accelerate around puberty. Despite this, there is a paucity of both data and treatment options for HAE in children in the United States. Our objective was to summarize the published data and perform a retrospective chart review on children with HAE to improve care of the child with the disease. A retrospective chart review study was performed after Institutional Review Board approval. A search of electronic medical records from 2001 to 2011 was performed for children aged 1 to 18 years with a confirmed diagnosis of HAE. Demographic patient information was obtained and analyzed. Twenty-five pediatric patients were identified with the diagnosis of HAE: 13 female and 12 male. The median age at diagnosis was seven years. The most common initial presenting symptom was swelling of the upper extremity, followed by abdominal pain, swelling of the face and/or lower extremity, and scrotal swelling. Three patients reported no previous symptoms and were diagnosed due to family history of HAE and positive laboratory testing. The majority of patients (84%) reported a family history of HAE. Accurate and timely diagnosis of HAE is imperative for children to prevent further morbidity and mortality associated with the disease.

Effect of wall thickness of 3D-printed models on resisting deformation from thermal forming in-office aligners.

BACKGROUND: Fabricating clear aligners by thermoforming three-dimensional printed dental models requires a high degree of accuracy. It is unknown whether model thickness affects the accuracy when used to thermoform aligners. PURPOSE: This research utilizes three-dimensional printed models made with differing wall thicknesses to determine its effect on their ability to withstand deformation during aligner fabrication. METHODS: A total of 50 models of different wall thickness (10 each of 0.5, 1.0, 1.5, 2.0 mm, and solid) were printed using model resin (Model V2, Formlabs) on a low-force stereolithography printer (Form 3B, Formlabs). Aligners were then fabricated using a thermal pressure forming machine (Biostar V, Great Lakes Dental Technologies) utilizing 25 s cycles to adapt 0.030″ acrylic sheets (Invisacryl, Great Lakes Dental Technologies), then removed from the models and sprayed with a contrast powder (Optispray, Dentsply Sirona) to aid in scanning with an intraoral scanner (CEREC Primescan, Dentsply Sirona). Each aligner's data was then compared to the original file used for printing with 3D comparison software (Geomagic Control X, 3D Systems). RESULTS: The results show model thickness greater than or equal to 2.0 mm produced clinically acceptable results within the margin of error (0.3 mm). A total of 0.5 mm thickness failed to withstand thermal forming in 4 of the 10 trials. A total of 0.5 mm produced 27.56% of results in tolerance, 1.0 mm produced 75.66% of results in tolerance, 1.5 mm had 80.38% of results in tolerance, 86.82% of 2 mm models were in tolerance, and solid had 96.45% of results in tolerance. CONCLUSION: Hollow models of thicknesses 2.0 mm and solid models produced clinically acceptable aligners while utilizing less resin per unit compared to solid models, thus being more cost effective, time efficient and eco-friendly. Therefore, a recommendation can be made to print hollow models with a shell thickness of greater than 2.0 mm for aligner fabrication.

Characterization of Antimicrobial Poly(Lactic Acid)- and Polyurethane-Based Materials Enduring Closed-Loop Recycling with Applications in Space.

Recent studies have shown that astronauts experience altered immune response behavior during spaceflight, resulting in heightened susceptibility to illness. Resources and resupply shuttles will become scarcer with longer duration spaceflight, limiting access to potentially necessary medical treatment and facilities. Thus, there is a need for preventative health countermeasures that can exploit in situ resource utilization technologies during spaceflight, such as additive manufacturing (i.e., 3D printing). The purpose of the current study was to test and validate recyclable antimicrobial materials compatible with additive manufacturing. Antimicrobial poly(lactic acid)- and polyurethane-based materials compatible with 3D printing were assessed for antimicrobial, mechanical, and chemical characteristics before and after one closed-loop recycling cycle. Our results show high biocidal efficacy (>90%) of both poly(lactic acid) and polyurethane materials while retaining efficacy post recycling, except for recycled-state polyurethane which dropped from 98.91% to 0% efficacy post 1-year accelerated aging. Significant differences in tensile and compression characteristics were observed post recycling, although no significant changes to functional chemical groups were found. Proof-of-concept medical devices developed show the potential for the on-demand manufacturing and recyclability of typically single-use medical devices using antimicrobial materials that could serve as preventative health countermeasures for immunocompromised populations, such as astronauts during spaceflight.

Developmental abnormalities in chicken embryos exposed to N-nitrosoatrazine.

Nitrate and atrazine (ATR) occur in combination in some drinking-water supplies and might react to form N-nitrosoatrazine (NNAT), which is reportedly more toxic than nitrate, nitrite, or ATR. Current evidence from population-based studies indicates that exposure to nitrate, nitrite, and nitrosatable compounds increases the risk of congenital defects and/or rate of embryo lethality. To test the hypothesis that NNAT induces malformations during embryogenesis, chicken embryos were examined for lethality and developmental abnormalities after treating fertilized eggs with 0.06-3.63 µg NNAT. After 5 d of incubation (Hamburger and Hamilton stage 27), 90% of embryos in NNAT-treated eggs were alive, of which 23% were malformed. Malformations included heart and neural-tube defects, caudal regression, gastroschisis, microphthalmia, anophthalmia, and craniofacial hypoplasia. The findings from this investigation suggest further studies are needed to determine the mechanisms underlying NNAT-induced embryotoxicity.

High-affinity folate receptor in cardiac neural crest migration: a gene knockdown model using siRNA.

Folate supplementation reduces the incidence of congenital heart defects, but the nature of this protective mechanism remains unclear. Immunolabeling demonstrated that the neural tube and neural crest (NC) cells were rich in the high-affinity folate receptor FOLR1and during the early stages of development FOLR1 was found principally in these cells. Suppression of Folr1 expression in the nascent cardiac NC by site-directed short-interfering RNA (siRNA) altered cardiac NC cell mitosis and subsequent migration patterns leading to abnormal development of the pharyngeal arch arteries (PAA) and outflow tract. qPCR analysis demonstrated that the siRNA treatment significantly reduced Folr1 24 hr after treatment. These treatments also significantly reduced mitosis in the neural tube, but adjacent, nontreated areas were unaffected. In summary, a brief reduction in the expression of Folr1 during a critical stage of NC development had long-term consequences for the development of the PAA and outflow tract.

Effect of immune complex formation on the distribution of a novel antibody to the ovarian tumor antigen CA125.

3A5 is a novel antibody that binds repeated epitopes within CA125, an ovarian tumor antigen that is shed into the circulation. Binding to shed antigen may limit the effectiveness of therapeutic antibodies because of unproductive immune complex (IC) formation and/or altered antibody distribution. To evaluate this possibility, we characterized the impact of shed CA125 on the in vivo distribution of 3A5. In vitro, 3A5 and CA125 were found to form ICs in a concentration-dependent manner. This phenomenon was then evaluated in vivo using quantitative whole-body autoradiography to assess the tissue distribution of (125)I-3A5 in an orthotopic OVCAR-3 tumor mouse model at different stages of tumor burden. Low doses of 3A5 (75 µg/kg) and pathophysiological levels of shed CA125 led to the formation of ICs in vivo that were rapidly distributed to the liver. Under these conditions, increased clearance of 3A5 from normal tissues was observed in mice bearing CA125-expressing tumors. Of importance, despite IC formation, 3A5 uptake by tumors was sustained over time. At a therapeutically relevant dose of 3A5 (3.5 mg/kg), IC formation was undetectable and distribution to normal tissues followed that of blood. In contrast, increased levels of radioactivity were observed in the tumors. These data demonstrate that CA125 and 3A5 do form ICs in vivo and that the liver is involved in their uptake. However, at therapeutic doses of 3A5 and clinically relevant CA125 levels, IC formation consumes only a minor fraction of 3A5, and tumor targeting seems to be unaffected.

Hyperthermia: malformations to chaperones.

Hyperthermia has been known to induce malformations in numerous animal models as well being associated with human abnormalities. This was apparent particularly when the hyperthermia exposure was during the early stages of neural development. Although it was recognized relatively early that these exposures induced cell death, the specific molecular mechanism of how a brief heat exposure was translated in to specific cellular functions remains largely unknown. While our understanding of the events that govern how cells react to heat, or stresses in general, has increased, there is much that remains undiscovered. In this brief review, animal and clinical observations are outlined as are some of the scientific explorations that were undertaken to characterize, define, and better understand the morphological, biochemical, and molecular effects of hyperthermia on the developing embryo.

Pre-Conditioning and Post-Operative Photobiomodulation Therapy by a Novel Light Patch System for Knee Arthroplasty: A Protocol for a Phase 1 Study.

Objective: To determine the potential efficacy and feasibility of photobiomodulation therapy (PBMT) before and after knee arthroplasty (KA) surgery. Background: Total knee replacements (total knee arthroplasty, TKA) are one of the most common and successful surgical interventions for osteoarthritis. Up to 20,000 knee replacement arthroplasties are performed in Australia annually. Although TKA aims to restore knee alignment and relieve pain in the long term, the initial post-operative period is difficult and rehabilitation is often hindered by persistent pain and swelling. A promising therapeutic approach, PBMT using a novel self-adhesive light patch system, may be feasible for reducing post-operative pain and swelling and aiding recovery. Materials and methods: This is an interventional clinical feasibility study protocol. Patients from a surgical waitlist will be invited to take part. PBMT will be applied for 30 min daily for 7 days pre-operatively using a novel light patch system (CareWear®) with both 450 nm (6.75 mW/cm2) and 640 nm (2.25 mW/cm2) microdiodes. Post-operative treatment will utilize the same device second daily for 1 week after removal of compression bandages. Results: Outcomes will be evaluated at seven time points: baseline at week 1 pre-operatively, 1 day before surgery, day 4 after surgery, weekly for a further 2 weeks, and fortnightly until 6 weeks post-hospital discharge. Outcome measures include the following: Numeric Pain Rating Scale, stair climb test, 30-sec chair stand test, timed up and go test, 40-m fast-paced walk test, modified Iowa Level of Assistance Scale, muscle strength, knee range of motion, Knee Injury and Osteoarthritis Outcome Score, and Lower Limb Functional Index. Conclusions: This study will provide an assessment of feasibility of using PBMT applied using a novel light patch system for management of pain symptoms and swelling, and aiding recovery of patients undergoing TKA. The results of this feasibility study will contribute to planning of the design and methods of a large clinical trial.

The root of dental anatomy: a case for naming Eustachius the "father of dental anatomy".

When one considers the names of those whose affect on dentistry reached far beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One name that deserves to be called among the pantheon of the greats is Bartholomaeus Eustachius. Eustachius was not the first to study the anatomy of the teeth and jaws, having been preceded by Da Vinci; however, he was the first to publish a treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir William Osler, the father of modern medicine, stated: "In Science, the credit goes to the man who convinces the world, not to whom the idea first occurs." The purpose of this paper is to show that Eustachius deserves to be named the father of dental anatomy.

Quantitative determination of humanized monoclonal antibody rhuMAb2H7 in cynomolgus monkey serum using a Generic Immunoglobulin Pharmacokinetic (GRIP) assay.

Preclinical pharmacokinetic (PK) assays are important to help evaluate the safety and efficacy of a potential biotherapeutic before clinical studies. The assay typically requires a biotherapeutic-specific reagent to minimize matrix effects especially when the host species are non-human primates such as cynomolgus monkeys and the biotherapeutic is a humanized monoclonal antibody (MAb). Recombinant humanized mAb 2H7 (rhuMAb2H7) binds to the extracellular domain of CD20 that is expressed on B cells and results in B cell depletion. It is currently being evaluated for its therapeutic potential in rheumatoid arthritis (RA) in clinical studies. During the early development of rhuMAb2H7, a cynomolgus monkey PK assay was needed to help assess the pharmacokinetic parameters of rhuMAb2H7 in a pilot cynomolgus monkey study. However, development of a cynomolgus monkey PK assay was challenging due to lack of rhuMAb2H7-specific reagents. Here we describe an alternative method for detection of rhuMAb2H7 in cynomolgus monkey serum using polyclonal antibodies against human IgGs. This assay quantifies rhuMAb2H7 in 10% cynomolgus monkey serum with high sensitivity, accuracy, and precision. This assay successfully supported the rhuMAb2H7 development, and has the potential to be used to quantify other humanized MAb biotherapeutics in serum from a variety of non-human species.

Timing of venous thromboembolism chemoprophylaxis after traumatic brain injury.

OBJECTIVES: Currently no national standard exists on optimal timing to initiate VTE chemoprophylaxis after traumatic brain injury (TBI). We designed this survey to assess current practice regarding the timing of VTE chemoprophylaxis after TBI. METHODS: All the EAST members were surveyed online. Participants reported demographics, and responses to questions regarding VTE chemoprophylaxis in TBI and timing of chemoprophylaxis in 2 hypothetical clinical scenarios of TBI. RESULTS: Three hundred and ninety-one full responses were collected (response rate 30.9%). Most respondents (75%) reported the decision to initiate VTE chemoprophylaxis with a consensus between the neurosurgery and trauma/critical care services. While 76% of respondents reported experience of seeing pulmonary embolism without chemoprophylaxis, 44% witnessed progression of TBI after VTE chemoprophylaxis. Approximately 50% considered their practice of VTE chemoprophylaxis in TBI patients to be conservative. Almost 50% reported no standardized protocol in their institutions. While 1/3 of the members believed guidelines exist, another 1/3 believed no guidelines available. Responses to two clinical scenarios showed various approaches regarding the timing of VTE chemoprophylaxis. CONCLUSIONS: Currently there is a wide variability in the practice patterns regarding the timing of VTE chemoprophylaxis in TBI patients. This survey reinforces the need for further investigation to guide clinical practice.

Species-dependent serum interference in a sandwich ELISA for Apo2L/TRAIL.

To support pre-clinical studies of Apo2L/TRAIL in rodents and non-human primates, a sandwich ELISA was developed using two mouse monoclonal anti-Apo2L/TRAIL antibodies. Mouse, rat, cynomolgus monkey, and chimpanzee serum at concentrations of > or =1% were found to interfere with accurate quantitation of Apo2L/TRAIL. Moreover, the characteristics of the serum interference for each species were different. In order to resolve the observed serum effect, studies were performed in which salts, detergents, and blocking proteins were added to the sample diluent, and optimized sample diluents that eliminated serum interference were developed for mouse, cynomolgus monkey, and chimpanzee serum. These buffers consisted of a base assay diluent (PBS/0.5% BSA/0.05% Tween-20/10 ppm ProClin 300) supplemented with: NaCl (mouse serum); NaCl, EDTA, CHAPS, bovine gamma globulin (BGG), and human IgG (cynomolgus monkey serum); and NaCl and EDTA (chimpanzee serum). Full characterization studies were performed for the "buffer" ELISA run in base assay diluent (intended for non-serum samples) as well as the assays optimized for mouse serum and cynomolgus monkey serum. Precision, accuracy, linearity, and specificity were found to be satisfactory. With the availability of a rabbit polyclonal antibody against Apo2L/TRAIL, a new pAb/mAb ELISA was developed. This assay was not only more sensitive by > or =6-fold, but it was also much less subject to serum interference.

The expression of the NR1-subunit of the NMDA receptor during mouse and early chicken development.

It has been suggested that homocysteine-induced defects are mediated by the inhibition of the N-methyl-d-aspartate (NMDA) receptor on neural crest cells. However, the majority of this work has been performed using the chicken embryo model. In an effort to better understand the molecular events involved a murine model of homocysteine-induced defects was sought. However, it has been previously shown that homocysteine failed to induce congenital defects in several strains of mouse. Therefore, in an effort to better understand the difference in the susceptibility between these two species we investigated the ontogeny of the NMDA receptor in the mouse and chicken. To determine the expression of the NMDA receptor we performed Western blot analysis using an antibody to the NR1-subunit of the NMDA receptor in both the chicken and mouse embryos. Further, we used RT-PCR to determine the temporal expression of this subunit in the murine embryos from gestational day 8.5 to 18.5 to confirm our Western blot analysis. Results from these studies demonstrated that the expression of the NMDA receptor was expressed during the early stages of development in the chick embryo but neither the transcript nor the protein was detected in mouse embryos until later in development. These results demonstrate that during the stages of neurulation and/or early heart development the expression of the NR1-subunit of the NMDA receptor was not detected. The expression of this gene increased and was detectable by gestational days 14.5-15.5 and continued to increase in its expression until term. Therefore, these experiments suggest that homocysteine-induced defects may be mediated via the NMDA receptor.