A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance.

Carbapenem resistance due to metallo-ß-lactamases (MBLs) such as the Verona integron-encoded metallo-ß-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel ß-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant Klebsiella pneumoniae isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both patients were analyzed using whole-genome sequencing. This analysis revealed that the pairs of isolates independently acquired point mutations in both the cirA and fiu genes, which encode siderophore receptors. These point mutations were remade in a laboratory strain of K. pneumoniae and resulted in a significant increase in the MIC of cefiderocol, even in the absence of a beta-lactamase enzyme or a penicillin-binding protein 3 (PBP3) mutation. While newer ß-lactam antibiotics remain an exciting addition to the antibiotic armamentarium, their use must be accompanied by diligent monitoring for the rapid development of resistance.

Loss of Ribosomal Protein Paralog Rpl22-like1 Blocks Lymphoid Development without Affecting Protein Synthesis.

Ribosomal proteins are thought to primarily facilitate biogenesis of the ribosome and its ability to synthesize protein. However, in this study, we show that Rpl22-like1 (Rpl22l1) regulates hematopoiesis without affecting ribosome biogenesis or bulk protein synthesis. Conditional loss of murine Rpl22l1 using stage or lineage-restricted Cre drivers impairs development of several hematopoietic lineages. Specifically, Tie2-Cre-mediated ablation of Rpl22l1 in hemogenic endothelium impairs the emergence of embryonic hematopoietic stem cells. Ablation of Rpl22l1 in late fetal liver progenitors impairs the development of B lineage progenitors at the pre-B stage and development of T cells at the CD44-CD25+ double-negative stage. In vivo labeling with O-propargyl-puromycin revealed that protein synthesis at the stages of arrest was not altered, indicating that the ribosome biogenesis and function were not generally compromised. The developmental arrest was associated with p53 activation, suggesting that the arrest may be p53-dependent. Indeed, development of both B and T lymphocytes was rescued by p53 deficiency. p53 induction was not accompanied by DNA damage as indicated by phospho-γH2AX induction or endoplasmic reticulum stress, as measured by phosphorylation of EIF2α, thereby excluding the known likely p53 inducers as causal. Finally, the developmental arrest of T cells was not rescued by elimination of the Rpl22l1 paralog, Rpl22, as we had previously found for the emergence of hematopoietic stem cells. This indicates that Rpl22 and Rpl22l1 play distinct and essential roles in supporting B and T cell development.

Design, Fabrication, and Characterization of Inkjet-Printed Organic Piezoresistive Tactile Sensor on Flexible Substrate.

In this paper, we propose a novel tactile sensor with a "fingerprint" design, named due to its spiral shape and dimensions of 3.80 mm × 3.80 mm. The sensor is duplicated in a four-by-four array containing 16 tactile sensors to form a "SkinCell" pad of approximately 45 mm by 29 mm. The SkinCell was fabricated using a custom-built microfabrication platform called the NeXus which contains additive deposition tools and several robotic systems. We used the NeXus' six-degrees-of-freedom robotic platform with two different inkjet printers to deposit a conductive silver ink sensor electrode as well as the organic piezoresistive polymer PEDOT:PSS-Poly (3,4-ethylene dioxythiophene)-poly(styrene sulfonate) of our tactile sensor. Printing deposition profiles of 100-micron- and 250-micron-thick layers were measured using microscopy. The resulting structure was sintered in an oven and laminated. The lamination consisted of two different sensor sheets placed back-to-back to create a half-Wheatstone-bridge configuration, doubling the sensitivity and accomplishing temperature compensation. The resulting sensor array was then sandwiched between two layers of silicone elastomer that had protrusions and inner cavities to concentrate stresses and strains and increase the detection resolution. Furthermore, the tactile sensor was characterized under static and dynamic force loading. Over 180,000 cycles of indentation were conducted to establish its durability and repeatability. The results demonstrate that the SkinCell has an average spatial resolution of 0.827 mm, an average sensitivity of 0.328 mΩ/Ω/N, expressed as the change in resistance per force in Newtons, an average sensitivity of 1.795 µV/N at a loading pressure of 2.365 PSI, and a dynamic response time constant of 63 ms which make it suitable for both large area skins and fingertip human-robot interaction applications.

Effect of additive manufacturing process and storage condition on the dimensional accuracy and stability of 3D-printed dental casts.

STATEMENT OF PROBLEM: Additively manufactured dental casts are gaining popularity as the digital workflow is adopted in dentistry. However, studies on their dimensional accuracy and stability under different storage conditions in the dental laboratory are lacking. PURPOSE: The purpose of this in vitro study was to compare the effects of different additive manufacturing processes and storage conditions on the dimensional accuracy and stability of 3D-printed dental casts. MATERIAL AND METHODS: A completely dentate maxillary typodont model was digitized 10 times with a dental laboratory laser scanner, and the standard tessellation language (STL) files were used to manufacture 3D-printed diagnostic casts with the digital light projection (DLP) 3D printer (Asiga MAX) and material jetting (MJ) 3D printer (ProJet 3510 DPPro). Twenty DLP-printed and 20 MJ-printed diagnostic casts were digitized within 24 hours of production. Subsequently, all 3D-printed diagnostic casts were stored for 3 months, either in closed laboratory boxes or in dental laboratory open-face plastic containers with direct exposure to full-spectrum balanced light. After 3-month storage, all 40 3D-printed casts were digitized again. All scanned files were compared with the corresponding STL files in a surface-matching software program. The dimensional accuracy was measured and compared by the root mean square (RMS, in µm). Repeated measures analysis of variance (ANOVA) was used to compare RMS values among the variables, and the Tukey honestly significant difference (HSD) test was used for post hoc multiple comparisons (α=.05). RESULTS: The casts produced from the DLP 3D printer had a significantly higher mean ±standard deviation RMS of 153.7 ±25.4 µm than those produced with the MJ 3D printer with RMS of 134.1 ±16.0 µm (P<.001). The storage condition (box storage versus light exposure) did not affect the accuracy of the DLP-printed casts (P=.615) or the MJ-printed casts (P=.999). When comparing all 3D-printed casts after 3-month storage, group DLP-3M-Lit had the highest mean ±standard deviation RMS of 163.0 ±26.5 µm, and group MJ-3M-Box had the lowest RMS of 132.8 ±16.9 µm. The DLP-printed casts stored under light exposure were significantly less accurate than the MJ-printed casts stored in the box (P=.048). DLP-printed casts stored under light exposure showed significant surface color change under visual inspection. CONCLUSIONS: The MJ 3D printer produced more accurate 3D-printed dental casts than the DLP 3D printer. After 3-month storage, the DLP-printed casts stored under light exposure were the least accurate, and the MJ-printed casts stored without light exposure were the most accurate. The surface color change of DLP-printed casts stored under light exposure after 3-month storage was evident.

Evaluation of esthetic parameters related to a single implant restoration by laypeople and dentists.

STATEMENT OF PROBLEM: Currently available assessment tools for evaluating the esthetic outcome of implant restorations consist of objective indices created for dentists. The investigation of esthetic parameters according to the patient's perspective is lacking. PURPOSE: The purpose of this observational study was to evaluate and compare the importance of different soft-tissue and restoration-related esthetic parameters for patients and clinicians. MATERIAL AND METHODS: A photoediting software program (Photoshop CC; Adobe Corp) was used to produce 10 photographs with modified smiles from the original photograph by altering 1 parameter of the pink esthetic score and white esthetic score (PES/WES) at a time. A total of 120 participants were recruited in the study, including 40 laypeople, 40 prosthodontists, and 40 periodontists. A total of 440 visual analog scale (VAS) values were obtained for each group to record participants' subjective esthetic assessments of all photographs (10 modified and 1 original photograph). Repeated-measures ANOVA and post hoc mean comparison (t grouping) were used to identify whether the individual alteration on the PES and WES indices was significant for each group. RESULTS: For the laypeople, color (hue and value) appeared to be the most important parameter. After color, the order of importance was as follows: root convexity along with soft-tissue color and texture, level of facial mucosa, distal papilla, mesial papilla, translucency or characterization, surface texture, and tooth form. For the periodontists, color (hue and value) was also the most important parameter, but it was not separable from a cluster of other parameters: level of facial mucosa, root convexity along with soft-tissue color and texture, mesial papilla, and distal papilla. For the prosthodontists, color (hue and value) and level of facial mucosa were the most important parameters affecting esthetic assessment, followed by root convexity along with soft-tissue color and texture, mesial papilla, and distal papilla. CONCLUSIONS: All groups graded color (hue and value) as the most important parameter affecting the esthetic outcome and the original unaltered photograph as the most esthetically pleasing image. All participants (laypeople and dental specialists) appeared to be able to perceive the same 5 parameters including color (hue and value), level of facial mucosa, mesial papilla, distal papilla, and root convexity along with soft-tissue color and texture that are negatively affecting esthetic outcomes. Except for color (hue and value), restoration-related esthetic parameters had a lesser effect on the overall esthetic assessments for all groups.

Effect of Statin Coadministration on the Risk of Daptomycin-Associated Myopathy.

Background: Daptomycin-associated myopathy has been identified in 2%-14% of patients, and rhabdomyolysis is a known adverse effect. Although risk factors for daptomycin-associated myopathy are poorly defined, creatine phosphokinase (CPK) monitoring and temporary discontinuation of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or "statins," has been recommended. Methods: We conducted a single-center, retrospective, matched case-control risk factor analysis in adult and pediatric patients from 2004 to 2015. Patients in whom myopathy (defined as CPK values above the upper limit of normal) developed during daptomycin treatment were matched 1:1 to no-myopathy controls with at least the same duration of therapy. Risk factors independently associated with myopathy were determined using multivariable conditional logistic regression. Secondary analysis was performed in patients with rhabdomyolysis, defined as CPK values ≥10 times the upper limit of normal. Results: Of 3042 patients reviewed, 128 (4.2%) were identified as having daptomycin-associated myopathy, 25 (0.8%) of whom had rhabdomyolysis; 121 (95%) of the 128 were adults, and the mean duration of therapy before CPK elevation was 16.7 days (range, 1-58 days). In multivariate analysis, deep abscess treatment (odds ratio, 2.80; P = .03), antihistamine coadministration (3.50; P = .03), and statin coadministration (2.60; P = .03) were independent risk factors for myopathy. Obesity (odds ratio, 3.28; P = .03) and statin coadministration (4.67; P = .03) were found to be independent risk factors for rhabdomyolysis, and older age was associated with reduced risk (0.97; P = .05). Conclusions: Statin coadministration with daptomycin was independently associated with myopathy and rhabdomyolysis. This is the first study to provide strong evidence supporting this association. During coadministration, we recommend twice-weekly CPK monitoring and consideration of withholding statins.

Posaconazole-Induced Pseudohyperaldosteronism.

A woman in her late 60s with disseminated histoplasmosis was treated with posaconazole because first-line therapies were not tolerated. She subsequently presented with decompensated heart failure, hypertension, and hypokalemia. Laboratory tests revealed low renin and aldosterone levels. A potential mechanism is inhibition of the enzyme 11ß-hydroxysteroid dehydrogenase 2, with resultant apparent mineralocorticoid excess.

Fabrication of an interim complete removable dental prosthesis with an in-office digital light processing three-dimensional printer: A proof-of-concept technique.

This report describes a proof of concept for fabricating an interim complete removable dental prosthesis with a digital light processing 3-dimensional (3D) printer. Although an in-office 3D printer can reduce the overall production cost for an interim complete removable dental prosthesis, the process has not been validated with clinical studies. This report provided a preliminary proof of concept in developing a digital workflow for the in-office additively manufactured interim complete removable dental prosthesis.

Integrating hinge axis approximation and the virtual facial simulation of prosthetic outcomes for treatment with CAD-CAM immediate dentures: A clinical report of a patient with microstomia.

This clinical report describes a digital workflow using extraoral digital photographs and volumetric datasets from cone beam computed tomography (CBCT) imaging to create a 3-dimensional (3D), virtual patient with photorealistic appearance. In a patient with microstomia, hinge axis approximation, diagnostic casts simulating postextraction alveolar ridge profile, and facial simulation of prosthetic treatment outcome were completed in a 3D, virtual environment. The approach facilitated the diagnosis, communication, and patient acceptance of the treatment of maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) of immediate dentures at increased occlusal vertical dimension.

Integrating a facial scan, virtual smile design, and 3D virtual patient for treatment with CAD-CAM ceramic veneers: A clinical report.

This clinical report describes a digital workflow using the virtual smile design approach augmented with a static 3-dimensional (3D) virtual patient with photorealistic appearance to restore maxillary central incisors by using computer-aided design and computer-aided manufacturing (CAD-CAM) monolithic lithium disilicate ceramic veneers.

Polyetherketoneketone (PEKK), a framework material for complete fixed and removable dental prostheses: A clinical report.

This clinical report demonstrates the use of polyetherketoneketone (PEKK) as a framework material with individually luted heat-pressed lithium disilicate glass-ceramic crowns for an implant-supported complete fixed dental prosthesis (ICFDP) and a conventional complete removable dental prosthesis (CRDP). This prosthesis design provides a non-computer-aided design and computer-aided manufacturing (CAD-CAM) option for the fabrication of ICFDPs and CRDPs with individualized ceramic crowns for optimal esthetics. The performance of PEKK as a framework material needs to be assessed in clinical trials.

Accuracy and reproducibility of virtual edentulous casts created by laboratory impression scan protocols.

STATEMENT OF PROBLEM: Although computer-aided design and computer-aided manufacturing (CAD-CAM) complete removable dental prostheses (CRDPs) have gained popularity, conventional impressions are still common for CAD-CAM CRDP treatment. These need to be digitized and converted into virtual edentulous casts with a laboratory impression scan protocol during prosthesis fabrication. How this can best be accomplished is unclear. PURPOSE: The purpose of this in vitro study was to compare the accuracy and reproducibility of virtual edentulous casts created by a dental laboratory laser scanner and a cone beam computed tomography (CBCT) scanner with a digitized master cast. MATERIAL AND METHODS: A master cast was digitized as the virtual reference cast. Ten polyvinyl siloxane impressions were made on the master cast and scanned with the dental laboratory laser scanner and CBCT scanner. The impressions were sprayed with antiglare spray and rescanned. Four groups of virtual study casts (N=40) were created from the impression scans. All virtual study casts and the reference cast were registered with surface-matching software, and the root mean square (RMS) values (representation of overall accuracy) and percentage of measurement data points within 1 standard deviation (SD) of mean RMS values (%, representation of overall reproducibility) among the 4 study groups were measured. Additionally, 95 numeric distance differences (representation of accuracy at each region) were measured in 5 distinct regions: the apex of the denture border, 6 mm from denture border, crest of the ridge, palate, and posterior palatal seal. The repeated-measures ANOVA and post hoc test (t grouping) were used to determine statistical differences (α=.05). RESULTS: The laboratory scanner group had a significantly larger RMS value (4.0 ±0.3 µm, P<.001) and smaller percentage of measurement data points within 1 SD of mean RMS value (77.5 ±1.0%, P<.001). The RMS values between the CBCT scanner (1.2 ±0.3 µm) and CBCT scanner-spray (1.1 ±0.2 µm) groups were not significantly different (P=.968), and the percentage of measurement data points within 1 SD of mean RMS values (90.1 ±1.1% versus 89.5 ±0.8%) were also not significantly different (P=.662). The numeric distance differences across 5 regions were affected by the scanning protocols (P<.001). The laboratory scanner and laboratory scanner-spray groups had significantly higher numeric distance differences at the apex of the denture border and crest of the ridge regions (P<.001). CONCLUSIONS: The CBCT scanner created more accurate and reproducible virtual edentulous casts, and the antiglare spray only significantly improved the accuracy and reproducibility of virtual edentulous casts created by the dental laboratory laser scanner. The accuracy of the virtual edentulous casts was different across 5 regions and was affected by the scanning protocols.

Rpl22 Loss Impairs the Development of B Lymphocytes by Activating a p53-Dependent Checkpoint.

Although ribosomal proteins facilitate the ribosome's core function of translation, emerging evidence suggests that some ribosomal proteins are also capable of performing tissue-restricted functions either from within specialized ribosomes or from outside of the ribosome. In particular, we have previously demonstrated that germline ablation of the gene encoding ribosomal protein Rpl22 causes a selective and p53-dependent arrest of ab T cell progenitors at the b-selection checkpoint. We have now identified a crucial role for Rpl22 during early B cell development. Germline ablation of Rpl22 results in a reduction in the absolute number of B-lineage progenitors in the bone marrow beginning at the pro­B cell stage. Although Rpl22-deficient pro­B cells are hyporesponsive to IL-7, a key cytokine required for early B cell development, the arrest of B cell development does not result from disrupted IL-7 signaling. Instead, p53 induction appears to be responsible for the developmental defects, as Rpl22 deficiency causes increased expression of p53 and activation of downstream p53 target genes, and p53 deficiency rescues the defect in B cell development in Rpl22-deficient mice. Interestingly, the requirement for Rpl22 in the B cell lineage appears to be developmentally restricted, because Rpl22-deficient splenic B cells proliferate normally in response to Ag receptor and Toll receptor stimuli and undergo normal class-switch recombination. These results indicate that Rpl22 performs a critical, developmentally restricted role in supporting early B cell development by preventing p53 induction.

Managing complications resulting from limited prosthetic space with a monolithic, multichromatic CAD-CAM implant-retained overdenture: A dental technique.

This article proposes a 2-visit clinical protocol to manage prosthodontic complications resulting from limited prosthetic space, using a monolithic, multichromatic computer-aided design and computer-aided manufacturing (CAD-CAM) acrylic resin implant overdenture. The advantages and limitations of using this approach are outlined and discussed.

Creation of a 3-dimensional virtual dental patient for computer-guided surgery and CAD-CAM interim complete removable and fixed dental prostheses: A clinical report.

This clinical report proposes a digital workflow using 2-dimensional (2D) digital photographs, a 3D extraoral facial scan, and cone beam computed tomography (CBCT) volumetric data to create a 3D virtual patient with craniofacial hard tissue, remaining dentition (including surrounding intraoral soft tissue), and the realistic appearance of facial soft tissue at an exaggerated smile under static conditions. The 3D virtual patient was used to assist the virtual diagnostic tooth arrangement process, providing patient with a pleasing preoperative virtual smile design that harmonized with facial features. The 3D virtual patient was also used to gain patient's pretreatment approval (as a communication tool), design a prosthetically driven surgical plan for computer-guided implant surgery, and fabricate the computer-aided design and computer-aided manufacturing (CAD-CAM) interim prostheses.

Cone beam computed tomography imaging as a primary diagnostic tool for computer-guided surgery and CAD-CAM interim removable and fixed dental prostheses.

This article describes a digital workflow using cone beam computed tomography imaging as the primary diagnostic tool in the virtual planning of the computer-guided surgery and fabrication of a maxillary interim complete removable dental prosthesis and mandibular interim implant-supported complete fixed dental prosthesis with computer-aided design and computer-aided manufacturing technology. Diagnostic impressions (conventional or digital) and casts are unnecessary in this proposed digital workflow, providing clinicians with an alternative treatment in the indicated clinical scenario.

Digital approach to planning computer-guided surgery and immediate provisionalization in a partially edentulous patient.

This report describes a digital approach for computer-guided surgery and immediate provisionalization in a partially edentulous patient. With diagnostic data obtained from cone-beam computed tomography and intraoral digital diagnostic scans, a digital pathway of virtual diagnostic waxing, a virtual prosthetically driven surgical plan, a computer-aided design and computer-aided manufacturing (CAD/CAM) surgical template, and implant-supported screw-retained interim restorations were realized with various open-architecture CAD/CAM systems. The optional CAD/CAM diagnostic casts with planned implant placement were also additively manufactured to facilitate preoperative inspection of the surgical template and customization of the CAD/CAM-fabricated interim restorations.

Maxillary and mandibular immediately loaded implant-supported interim complete fixed dental prostheses on immediately placed dental implants with a digital approach: A clinical report.

This clinical report describes the treatment of maxillary and mandibular immediate implant placement and immediately loaded implant-supported interim complete fixed dental prostheses with a contemporary digital approach. The virtual diagnostic tooth arrangement eliminated the need for a customized radiographic template, and the diagnostic data collection required for computer-guided surgery (digital diagnostic impressions, digital photographs, and a cone beam-computed tomography [CBCT] scan) was completed in a single visit with improved workflow efficiency. Computer-aided design and computer-aided manufacturing (CAD/CAM)-fabricated surgical templates and interim prosthesis templates were made in a dental laboratory to facilitate computer-guided surgery and the immediate loading process.

Use of intraoral digital scanning for a CAD/CAM-fabricated milled bar and superstructure framework for an implant-supported, removable complete dental prosthesis.

This report describes a clinical technique for fabricating a maxillary implant-supported, removable complete dental prosthesis by using an intraoral digital scanner to register implant positions and soft tissue morphology. The presented technique uses computer-aided design/computer-aided manufacturing (CAD/CAM) technology with a subtractive manufacturing process to fabricate a milled bar (infrastructure framework) and an additive process to fabricate a friction fit, superstructure framework. This digital restorative pathway may decrease patient discomfort and reduce the labor associated with fabricating implant-supported, removable complete dental prostheses.