Nuclear magnetic resonance diffraction with subangstrom precision.

We have combined ultrasensitive force-based spin detection with high-fidelity spin control to achieve NMR diffraction (NMRd) measurement of ~2 million [Formula: see text]P spins in a [Formula: see text] volume of an indium-phosphide (InP) nanowire. NMRd is a technique originally proposed for studying the structure of periodic arrangements of spins, with complete access to the spectroscopic capabilities of NMR. We describe two experiments that realize NMRd detection with subangstrom precision. In the first experiment, we encode a nanometer-scale spatial modulation of the z-axis magnetization of [Formula: see text]P spins and detect the period and position of the modulation with a precision of <0.8 Å. In the second experiment, we demonstrate an interferometric technique, utilizing NMRd, to detect an angstrom-scale displacement of the InP sample with a precision of 0.07 Å. The diffraction-based techniques developed in this work extend the Fourier-encoding capabilities of NMR to the angstrom scale and demonstrate the potential of NMRd as a tool for probing the structure and dynamics of nanocrystalline materials.

Impact of continuous-flow mechanical circulatory support on cerebrospinal fluid motility.

BACKGROUND: Mechanical circulatory support (MCS), including ventricular assist devices (VADs), have emerged as promising therapeutic alternatives for end-stage congestive heart failure (CHF). The latest generation of these devices are continuous flow (CF) blood pumps. While there have been demonstrated benefits to patient outcomes due to CF-MCS, there continue to be significant clinical challenges. Research to-date has concentrated on mitigating thromboembolic risk (stroke), while the downstream impact of CF-MCS on the cerebrospinal fluid (CSF) flow has not been well investigated. Disturbances in the CSF pressure and flow patterns are known to be associated with neurologic impairment and diseased states. Thus, here we seek to develop an understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. METHODS: We built and validated a computational framework using lumped parameter modeling of cardiovascular, cerebrovascular physics, CSF dynamics, and autoregulation. A sensitivity analysis was performed to confirm robustness of the modeling framework. Then, we characterized the impact of CF-MCS on the CSF and investigated cardiovascular conditions of healthy and end-stage heart failure. RESULTS: Modeling results demonstrated appropriate hemodynamics and indicated that CSF pressure depends on blood flow pulsatility more than CSF flow. An acute equilibrium between CSF production and absorption was observed in the CF-MCS case, characterized by CSF pressure remaining elevated, and CSF flow rates remaining below healthy, but higher than CHF states. CONCLUSION: This research has advanced our understanding of the impact of CF-MCS on CSF dynamics and cerebral hemodynamics.

Therapy plans for therapeutic apheresis in Epic HealthLink.

BACKGROUND: A common required duty of pathology resident physicians while rotating on transfusion medicine is the medical oversight of the therapeutic apheresis service. A task often performed on this clinical medicine service is formulating and writing orders for therapeutic apheresis procedures. The EpicCare tool called the therapy plan provides unique advantages over a standard electronic order set for therapeutic apheresis. MATERIALS AND METHODS: Transfusion medicine physicians, apheresis nurses, pharmacists, and information technology professionals collaborated to create therapy plans for three therapeutic apheresis procedures: plasmapheresis, red cell exchange, and photopheresis. RESULTS: Therapy plans were implemented and have been well-received for several years. Over a six-year time period, a total of 613 therapy plans were created and signed. We speculate that this implementation may have increased both physician efficiency and patient safety. CONCLUSION: This article reports our experience using therapy plans in EpicCare in order to raise awareness of this tool and to serve as an encouragement for wider adoption.

Postural Control Deficits After Repetitive Soccer Heading.

OBJECTIVE: To determine the acute effects of repetitive soccer heading on postural control. DESIGN: Prospective study; participants were divided into 2 groups: a soccer heading group and a control group. SETTING: Biomechanics laboratory. PARTICIPANTS: One hundred sixty participants, including youth (age = 13.0 ± 0.8 years), high school (age = 17.2 ± 1.0 years), and collegiate (age = 20.2 ± 1.3 years) male and female soccer players, participated in this study. INTERVENTIONS: Participants in the soccer heading group performed 12 soccer headers (initial velocity = 11.2 m/s). Postural control testing was performed both before (PRE) and immediately after (POST) the purposeful soccer headers. Control participants performed postural control testing PRE and POST a 15-minute wait period. During postural control testing, participants were asked to stand on the MobileMat (Tekscan Inc, Boston, Massachusetts) for two 2-minute intervals with their hands on their hips and their feet together with one eyes-open and one eyes-closed trial. MAIN OUTCOME MEASURES: Using the center-of-pressure data, 95% area, sway velocity, and ApEn were calculated. Multilevel linear models were used to analyze the effects of age, sex, group, condition, and concussion history simultaneously. RESULTS: Participants in the soccer heading group had significantly higher sway velocity POST than participants in the control group after controlling for age, sex, concussion history, condition, and PRE (t = -3.002; P = 0.003; 95% confidence interval, -0.482 to -0.100). There were no significant differences from PRE to POST for 95% area, M/L ApEn, and A/P ApEn. CONCLUSIONS: Repetitive soccer heading does not affect most postural control measures, even among youth athletes. However, sway velocity increased after heading relative to control participants independent of age, sex, and concussion history.

Ultralow Dissipation Patterned Silicon Nanowire Arrays for Scanning Probe Microscopy.

In recent years, self-assembled semiconductor nanowires have been successfully used as ultrasensitive cantilevers in a number of unique scanning probe microscopy (SPM) settings. We describe the fabrication of ultralow dissipation patterned silicon nanowire (SiNW) arrays optimized for scanning probe applications. Our fabrication process produces ultrahigh aspect ratio vertical SiNWs that exhibit exceptional force sensitivity. The highest sensitivity SiNWs have thermomechanical noise-limited force sensitivity of [Formula: see text] at room temperature and [Formula: see text] at 4 K. To facilitate their use in SPM, the SiNWs are patterned within 7 µm from the edge of the substrate, allowing convenient optical access for displacement detection.

Radon and moisture impacts from interventions integrated with housing energy retrofits.

Energy retrofits can reduce air exchange, raising the concern of whether indoor radon and moisture levels could increase. This pre/post-intervention study explored whether simple radon interventions implemented in conjunction with energy retrofits can prevent increases in radon and moisture levels. Treatment homes (n = 98) were matched with control (no energy retrofits or radon intervention) homes (n = 12). Control homes were matched by geographic location and foundation type. t-tests were used to determine whether post-energy retrofit radon and moisture level changes in treatment homes significantly differed from those in control homes. The radon interventions succeeded in preventing statistically significant increases in first floor radon using arithmetic (p = 0.749) and geometric means (p = 0.120). In basements, arithmetic (p = 0.060) and geometric (p = 0.092) mean radon levels statistically significantly increased, consistent with previous studies which found that basement radon levels may increase even if first floor levels remain unchanged. Changes in infiltration were related to changes in radon (p = 0.057 in basements; p = 0.066 on first floors). Only 58% of the change in infiltration was due to air sealing, with the rest due to weather changes. There was no statistically significant association between air sealing itself and radon levels on the first floor (p = 0.664). Moisture levels also did not significantly increase.

Therapeutic plasma exchange for exogenous insulin antibody syndrome in combined variable immunodeficiency: a case report.

A 32-year-old male with type I diabetes presented with profound hypoglycemia due to exogenous insulin antibody syndrome in the setting of newly-diagnosed common variable immunodeficiency. Immunomodulatory therapy was not initially effective, but after the initiation of plasma exchange hypoglycemia resolved, and glucose lability improved.

Neuroplastic changes in anterior cruciate ligament reconstruction patients from neuromechanical decoupling.

The purpose of this study was to identify how the brain simultaneously perceives proprioceptive input during joint loading in anterior cruciate ligament reconstruction (ACLR) patients, when compared to healthy controls. Seventeen ACLR patients (ACLR) and seventeen controls (CONT) were tested for the somatosensory cortical activation using electroencephalography (EEG) while measuring knee laxity using a knee arthrometer. The relationship between cortical activation and joint laxity within group was also examined. The ACLR patients had increased cortical activation (36.4% ± 11.5%) in the somatosensory cortex during early loading (ERD1) to the injured limb compared to the CONT's matched limb (25.3% ± 13.2%, P = 0.013) as well as compared to the noninjured limb (25.1% ± 14.2%, P = 0.001). Higher somatosensory cortical activity during midloading (ERD2) to the ACLR knee positively correlated with knee laxity (mm) during early loading (LAX1, r = 0.530), midloading (LAX2, r = 0.506), total anterior loading (LAXA, r = 0.543), and total antero-posterior loading (LAXT, r = 0.501), while the noninjured limb revealed negative correlations between ERD1 and LAXA (r = -0.534) as well as between ERD2 and LAX2 (r = -0.565). ACLR patients demonstrate greater brain activation during joint loading in the injured knees when compared to healthy controls' matched knees as well as contralateral healthy knees, while the CONT group shows similar brain activation patterns during joint loading between limbs. These different neural activation strategies may indicate neuromechanical decoupling following an ACL reconstruction and evidence of altered sensorimotor perception and control of the knee (neuroplasticity), which may be critical to address after surgery for optimal neuromuscular control and patients' outcomes.

Analysis of Shoulder Complex Function After Posterior Spinal Fusion in Adolescents With Idiopathic Scoliosis.

BACKGROUND: Nonsurgically treated patients with AIS demonstrate altered scapular kinematics and decreased patient-reported shoulder function compared with typically developing adolescents. It is unknown whether surgical correction of the spine deformity has beneficial or detrimental effects on scapulothoracic joint function, as previous assessments of shoulder function following surgery have only focused on humerothoracic motion. The objective of this study was to perform a comprehensive analysis of scapular kinematics before and after PSF and compare postoperative scapular kinematics in AIS to those of a typically developing cohort. METHODS: Typically developing adolescents (n=33) and patients with AIS (n=20) with a planned PSF surgery were recruited. Motion capture was used to analyze scapular kinematics at rest and in full abduction. AIS subjects were evaluated before surgery and at a 6-month follow-up. Individual changes following surgery were assessed, and postoperative scapular kinematics were compared with the typically developing subjects. RESULTS: Patients with AIS patients in this study demonstrated significant losses of scapulothoracic range of motion for the convex side shoulder and gains of scapulothoracic range of motion for the concave side shoulder following PSF. When compared with typically developing adolescents, the resting scapular position of the postoperative AIS group seemed normalized, but the AIS group still exhibited altered scapular motion, particularly along the upward rotation and tilt axes. CONCLUSIONS: Patients with AIS demonstrated significant changes at the scapulothoracic joint following PSF. Compared with typically developing adolescents, scapular resting position normalized, but the AIS group still demonstrated altered scapular kinematics, including patterns associated with shoulder pathology. The results of this study will inform the course of short-term postoperative rehabilitation by addressing the upper extremity implications of PSF for individuals with AIS. LEVEL OF EVIDENCE: Level III.

The influence of acute elevations in plasma osmolality and serum sodium on sympathetic outflow and blood pressure responses to exercise.

Elevated plasma osmolality (pOsm) has been shown to increase resting sympathetic nerve activity in animals and humans. The present study tested the hypothesis that increases in pOsm and serum sodium (sNa+) concentration would exaggerate muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to handgrip (HG) exercise and postexercise ischemia (PEI). BP and MSNA were measured during HG followed by PEI before and after a 23-min hypertonic saline infusion (HSI-3% NaCl). Eighteen participants (age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed the protocol; pOsm and sNa+ increased from pre- to post-HSI (285 ± 1 to 291 ± 1 mosmol/kg H2O; 138.2 ± 0.3 to 141.3 ± 0.4 mM; P < 0.05 for both). Resting mean BP (90 ± 2 vs. 92 ± 1 mmHg) and MSNA (11 ± 2 vs. 15 ± 2 bursts/min) were increased pre- to post-HSI ( P < 0.05 for both). Mean BP responses to HG (106 ± 2 vs. 111 ± 2 mmHg, P < 0.05) and PEI (102 ± 2 vs. 107 ± 2 mmHg, P < 0.05) were higher post-HSI. Similarly, MSNA during HG (20 ± 2 vs. 29 ± 2 bursts/min, P < 0.05) and PEI (19 ± 2 vs. 24 ± 3 bursts/min, P < 0.05) were greater post-HSI. In addition, the change in MSNA was greater post-HSI during HG (Δ9 ± 2 vs. Δ13 ± 3 bursts/min, P < 0.05). A second set of participants ( n = 13, age 23 ± 1 yr; BMI 24 ± 1 kg/m2) completed a time control (TC) protocol consisting of quiet rest instead of an infusion. The TC condition yielded no change in resting sNa+, pOsm, mean BP, or MSNA (all P > 0.05); responses to HG and PEI were not different pre- to post-quiet rest ( P > 0.05). In summary, acutely increasing pOsm and sNa+ exaggerates BP and MSNA responses during HG exercise and PEI. NEW & NOTEWORTHY Elevated plasma osmolality has been shown to increase resting sympathetic activity and blood pressure. This study provides evidence that acute elevations in plasma osmolality and serum sodium exaggerated muscle sympathetic nerve activity and blood pressure responses during exercise pressor reflex activation in healthy young adults.

Shoulder Complex Mechanics in Adolescent Idiopathic Scoliosis and Their Relation to Patient-perceived Function.

BACKGROUND: Proper contribution of the scapulothoracic joint is necessary for adequate shoulder complex function. Associations between trunk shape and abnormal scapular kinematics and subsequent shoulder dysfunction have been established; however, the extent of shoulder dysfunction in adolescent idiopathic scoliosis (AIS) is still poorly understood. The purpose of this study was to perform a comprehensive analysis of scapular kinematics during multiplanar arm motion in patients with AIS and compare kinematics and patient-reported function with that of a typically developing cohort. METHODS: Typically developing adolescents (n=33) and patients with AIS (n=26) with no history of spine or shoulder surgery were recruited for this study. A 3-dimensional optoelectronic motion capture system was used to analyze scapular kinematics in 4 positions: rest, full abduction, forward reach, and hand to spine. Subjects in each group also completed the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire as a measure of patient-reported function. RESULTS: The convex shoulders of the patients with AIS exhibited deficits in scapular upward rotation and posterior tilt in all positions and reduced protraction range of motion during reaching. The AIS group also reported worse patient-perceived shoulder function than the typically developing group; however, this dysfunction was not related to specific scapular kinematic patterns. CONCLUSIONS: Patients with AIS show alterations in scapular kinematics that are associated with shoulder pathology. Despite displaying an unaffected ability to place the hand in space, the underlying joint mechanics place these adolescents at risk for future pathology. Accordingly, consideration of scapulothoracic and glenohumeral joint function is warranted in the treatment of AIS. LEVEL OF EVIDENCE: Level III-cross-sectional comparison.

Sex and age differences in head acceleration during purposeful soccer heading.

Differences in head-neck segment mass, purposeful heading technique, and cervical strength and stiffness may contribute to differences in head accelerations across sex and age. The purpose of this study was to compare head acceleration across sex and age (youth [12-14 years old], high school and collegiate) during purposeful soccer heading. One-hundred soccer players (42 male, 58 female, 17.1 ± 3.5 years, 168.5 ± 20.3 cm, 61.5 ± 13.7 kg) completed 12 controlled soccer headers at an initial ball velocity of 11.2 m/s. Linear and rotational accelerations were measured using a triaxial accelerometer and gyroscope and were transformed to the head centre-of-mass. A MANOVA revealed a significant multivariate main effect for sex (Pillai's Trace = .165, F(2,91) = 11.868, p < .001), but not for age (Pillai's Trace = .033, F(4,182) = 0.646, p = .630). Peak linear and rotational accelerations were higher in females (40.9 ± 13.3 g; 3279 ± 1065 rad/s2) than males (27.6 ± 8.5 g, 2219 ± 823 rad/s2). These data suggest that under controlled soccer heading conditions, females may be exposed to higher head accelerations than males.

Standardization of transfusion practice in organ donors using the Digital Intern, an electronic decision support algorithm.

BACKGROUND: Prospective clinical trials support restrictive thresholds for red blood cell (RBC) transfusion. Nonsurvivable donors are a major source of organs for transplantation. The Digital Intern (DI) is a computer algorithm to standardize donor care that includes a more restrictive transfusion threshold. The impact of standardized and restrictive RBC transfusion in organ donors, as determined by the DI, has not been reported. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study to compare the transfusion practice of the DI (n = 100) to a historic group of physician-managed donors (n = 90). Transfusion rates, the number of units transfused, and pretransfusion laboratory values were compared between groups. The variability of these parameters was also compared between groups. Finally, the number of transplanted organs per donor in each group was compared. RESULTS: The mean time as a donor was 25.9 ± 15.2 hours and was not different between the groups. In the DI group 19% were transfused compared to 26% in the control group (p = 0.3). The number of units transfused was less in the DI group (1 unit vs. 2 units per transfusion, p = 0.03) and the pretransfusion hematocrit was lower in the DI group (23% vs. 27%, p = 0.01). The variability in the latter two parameters was significantly lower in the DI group. The number of transplanted organs per donor was similar in both groups (3.24 [DI] vs. 3.03 [control], p = 0.37). CONCLUSION: The DI provides a more standardization transfusion practice in organ donors and reduces blood use without compromising transplantable organs.

Effect of Footwear on Dynamic Stability during Single-leg Jump Landings.

Barefoot and minimal footwear running has led to greater interest in the biomechanical effects of different types of footwear. The effect of running footwear on dynamic stability is not well understood. The purpose of this study was to compare dynamic stability and impact loading across 3 footwear conditions; barefoot, minimal footwear and standard running shoes. 25 injury free runners (21 male, 4 female) completed 5 single-leg jump landings in each footwear condition. Dynamic stability was assessed using the dynamic postural stability index and its directional components (mediolateral, anteroposterior, vertical). Peak vertical ground reaction force and vertical loadrates were also compared across footwear conditions. Dynamic stability was dependent on footwear type for all stability indices (ANOVA, p<0.05). Post-hoc tests showed dynamic stability was greater when barefoot than in running shoes for each stability index (p<0.02) and greater than minimal footwear for the anteroposterior stability index (p<0.01). Peak vertical force and average loadrates were both dependent on footwear (p≤0.05). Dynamic stability, peak vertical force, and average loadrates during single-leg jump landings appear to be affected by footwear type. The results suggest greater dynamic stability and lower impact loading when landing barefoot or in minimal footwear.

Cutting edge: a TLR9 cytoplasmic tyrosine motif is selectively required for proinflammatory cytokine production.

Compartmentalization of nucleic acid sensing TLR9 has been implicated as a mechanism to prevent recognition of self nucleic acid structures. Furthermore, recognition of CpG DNA in different endosomal compartments leads to the production of the proinflammatory cytokine TNF-α, or type I IFN. We previously characterized a tyrosine-based motif at aa 888-891 in the cytoplasmic tail of TLR9 important for appropriate intracellular localization. In this article, we show that this motif is selectively required for the production of TNF, but not IFN. In response to CpG DNA stimulation, the proteolytically processed 80-kDa fragment is tyrosine phosphorylated. Although Y888 is not itself phosphorylated, the structure of this motif is necessary for both TLR9 phosphorylation and TNF-α production in response to CpG DNA. We conclude that bifurcation in TLR9 signaling is regulated by a critical tyrosine motif in the cytoplasmic tail.

Discovery of Broad-Spectrum Herpes Antiviral Oxazolidinone Amide Derivatives and Their Structure-Activity Relationships.

Herpesvirus infections are ubiquitous, with over 95% of the adult population infected by at least one strain. While most of these infections resolve without treatment in healthy individuals, they can cause significant morbidity and mortality in immunocompromised, stem cell, or organ transplant patients. Current nucleoside standards of care provide meaningful benefit but are limited due to poor tolerability, resistance, and generally narrow spectrum of activity. Herpesviruses share a conserved DNA polymerase, the inhibition of which is validated as an effective strategy to disrupt viral replication. By utilizing a non-nucleoside inhibitor of the viral DNA polymerase, we sought to develop agents covering multiple herpesviruses (e.g., CMV, VZV, HSV1/2, EBV, and HHV6). Herein is described the invention of an oxazolidinone class of broad-spectrum non-nucleoside herpes antiviral inhibitors. A lead compound (42) with potent biochemical and broad-spectrum cellular activity was found to be efficacious in murine models against both HSV-1 and CMV infection.

Heterozygous carriage of a dysfunctional Toll-like receptor 9 allele affects CpG oligonucleotide responses in B cells.

Toll-like receptors (TLR) are employed by the innate immune system to detect microbial pathogens based on conserved microbial pathogen molecules. For example, TLR9 is a receptor for CpG-containing microbial DNA, and its activation results in the production of cytokines and type I interferons from human B cells and plasmacytoid dendritic cells, respectively. Both are required for mounting an efficient antibacterial or antiviral immune response. These effects are mimicked by synthetic CpG oligodeoxynucleotides (ODN). Although several hyporesponsive TLR9 variants have been reported, their functional relevance in human primary cells has not been addressed. Here we report a novel TLR9 allele, R892W, which is hyporesponsive to CpG ODN and acts as a dominant-negative in a cellular model system. The R892W variant is characterized by increased MyD88 binding and defective co-localization with CpG ODN. Whereas primary plasmacytoid dendritic cells isolated from a heterozygous R892W carrier responded normally to CpG by interferon-α production, carrier B cells showed impaired IL-6 and IL-10 production. This suggests that heterozygous carriage of a hyporesponsive TLR9 allele is not associated with complete loss of TLR9 function but that TLR9 signals elicited in different cell types are regulated differently in human primary cells.

Traditional biochemical assays for studying toll-like receptor 9.

Understanding the mechanistic basis of receptor activation and regulation can offer therapeutic targets for disease treatment. Evidence is emerging for a role of the normally foreign responsive Toll-like receptors (TLRs) in the development of autoimmunity through response to self-patterns. Regulatory mechanisms governing this class of receptors are poorly understood, and failures within this system likely contribute to development of autoimmunity. In this article, we review biochemical assays used to study one of the self-pattern responsive TLRs, TLR9, and suggest that these studies are critical for development of new targets for autoimmune therapies.

Effect of elastic taping on postural control deficits in subjects with healthy ankles, copers, and individuals with functional ankle instability.

BACKGROUND: Ankle sprains are the most common injury among physically active people, with common sequelae including repeated episodes of giving way, termed functional ankle instability. Copers are a cohort in ankle research comprised of those who have sprained their ankle but have not suffered any further dysfunction. The use of an elastic tape, Kinesio Tape, in sports medicine practice has recently gained popularity and may help improve postural control deficits related to functional ankle instability. The purpose of this study was to examine the immediate and prolonged effects of Kinesio Taping on postural control in healthy, coper, and unstable ankles as measured through single-limb balance on a force plate. METHODS: Sixty physically active, college-aged participants (72.5 ± 9.7 cm, 74.2 ± 16.2 kg, 21.5 ± 2.6 years) were stratified into healthy, coper, or unstable groups using the Cumberland Ankle Instability Tool (CAIT) combined with their history of ankle injury. Dependent variables included time-to-boundary (TTB) measures and traditional center of pressure (COP) measures in both the mediolateral (frontal) and anteroposterior (sagittal) planes. Testing was performed prior to tape application, immediately after application of the tape, 24 hours following tape application, and immediately after tape removal. RESULTS: Significant differences between groups were observed for COP standard deviation and range in the sagittal plane. Significant differences between tape conditions for TTB absolute minima and standard deviation were also noted. Post hoc testing revealed large to medium effect sizes for the group differences and very small effect sizes for the differences between conditions. CONCLUSIONS: Our study did not reveal decisively relevant changes following application of Kinesio Tape to the ankle. However, we did observe sagittal plane postural control deficits in subjects with ankle instability measured through summary COP variables over 20-second trials. CLINICAL RELEVANCE: Ankle instability is a concern for many clinicians. Kinesio Taping, although a popular form of clinical intervention, remains understudied. Evidence from this study does not support the use of Kinesio Taping for improving postural control deficits in those with ankle instability.

Randomized, controlled clinical trial of bilayer ceramic and metal-ceramic crown performance.

PURPOSE: Analyzing the clinical performance of restorative materials is important, as there is an expectation that these materials and procedures will restore teeth and do no harm. The objective of this research study was to characterize the clinical performance of metal-ceramic crowns, core ceramic crowns, and core ceramic/veneer ceramic crowns based on 11 clinical criteria. MATERIALS AND METHODS: An IRB-approved, randomized, controlled clinical trial was conducted as a single-blind pilot study. The following three types of full crowns were fabricated: (1) metal-ceramic crown (MC) made from a Pd-Au-Ag-Sn-In alloy (Argedent 62) and a glass-ceramic veneer (IPS d.SIGN veneer); (2) non-veneered (glazed) lithium disilicate glass-ceramic crown (LDC) (IPS e.max Press core and e.max Ceram Glaze); and (3) veneered lithia disilicate glass-ceramic crown (LDC/V) with glass-ceramic veneer (IPS Empress 2 core and IPS Eris). Single-unit crowns were randomly assigned. Patients were recalled for each of 3 years and were evaluated by two calibrated clinicians. Thirty-six crowns were placed in 31 patients. A total of 12 crowns of each of the three crown types were studied. Eleven criteria were evaluated: tissue health, marginal integrity, secondary caries, proximal contact, anatomic contour, occlusion, surface texture, cracks/chips (fractures), color match, tooth sensitivity, and wear (of crowns and opposing enamel). Numerical rankings ranged from 1 to 4, with 4 being excellent, and 1 indicating a need for immediate replacement. Statistical analysis of the numerical rankings was performed using a Fisher's exact test. RESULTS: There was no statistically significant difference between performance of the core ceramic crowns and the two veneered crowns at year 1 and year 2 (p > 0.05). All crowns were rated either as excellent or good for each of the clinical criteria; however, between years 2 and 3, gradual roughening of the occlusal surface occurred in some of the ceramic-ceramic crowns, possibly caused by dissolution and wear of the glaze. Statistically significant differences in surface texture (p= 0.0013) and crown wear (p= 0.0078) were found at year 3 between the metal-ceramic crowns and the lithium-disilicate-based crowns. CONCLUSION: Based on the 11 criteria, the clinical performance of ceramic-ceramic crowns was comparable to that of the metal-ceramic crowns after 2 years; however, gradual roughening occurred between years 2 and 3, which resulted in differences in surface texture and wear.