Faculty Bibliography
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165
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
PMID: 32972995
ISSN: 1095-9203
CID: 5065062
Non-silicate nanoparticles for improved nanohybrid resin composites
OBJECTIVE:Zirconia and alumina nanoparticles were coated with a silica-rich layer (ALSI and ZRSI) and used to prepare experimental nanohybrid resin composites, which were characterized and compared to a control commercial resin composite (Filtek Z350 XT). METHODS:) were also tested after 15 K thermal cycles. Data were analyzed using one-way or two-way ANOVA and Tukey's test (α = 0.05). RESULTS:. SIGNIFICANCE/CONCLUSIONS:ALSI and ZRSI generated nanohybrid resin composites with improved and/or more stable physical properties compared with nanosilica-based and commercial composites. This study suggests that changing the composition of nanofillers is a simple method to enhance the performance of nanohybrid composites.
PMID: 32758374
ISSN: 1879-0097
CID: 4572862
Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study
BACKGROUND:Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS:A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS:The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION/CONCLUSIONS:One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.
PMID: 32253678
ISSN: 1936-0541
CID: 4386552
Journal of biomedical materials research. Part B, Applied biomaterials. 2020:108(5):1868-1878.DOI: 10.1002/jbm.b.34528
In vivo efficacy of calcium phosphate-based synthetic-bone-mineral on bone loss resulting from estrogen and mineral deficiencies
Osteopenia and osteoporosis affect over 40 million US adults 50 years and older. Both diseases are strongly influenced by estrogen and nutritional-mineral deficiencies. This study investigates the efficacy of orally delivered synthetic-bone-mineral (SBM), a newly developed calcium phosphate based biomaterial, on reversing bone loss induced by these two critical deficiencies. Thirty 3-month-old female rats were randomly allocated to either control-sham surgery on normal diet; or one of the four experimental groups: Sham surgery on a low mineral diet (LMD), ovariectomized (OVX) on LMD, OVX on LMD with SBM with/without fluoride (F). The rats were sacrificed after 6 months, at 9-month-old. After 6 months, although all groups lost bone mineral density relative to controls, the supplemented OVX rats showed higher bone mineral density than their unsupplemented counterparts. The 2 SBM supplemented groups improved bone loading capacity by 28.1 and 35.4% compared to the OVX LMD group. Bones from supplemented rats exhibited higher inorganic/organic ratios. The addition of F did not have a significant influence on bone loss. Our findings suggest that SBM supplement is effective in maintaining bone health and offsetting the deleterious effects of estrogen and/or mineral deficiencies on bone density, microarchitecture, and strength.
PMID: 31840930
ISSN: 1552-4981
CID: 4242092
Journal of the mechanical behavior of biomedical materials. 2020:105.DOI: 10.1016/j.jmbbm.2020.103722
Inverse correlations between wear and mechanical properties in biphasic dental materials with ceramic constituents
The objective of this study is to elucidate the interdependence of competing mechanical degradation processes in biphasic dental materials with ceramic constituents in the region of high-pressure occlusal loading. It is hypothesized that wear resistance in this region correlates inversely with basic material parameters (modulus, hardness, toughness, strength) evaluated from 'standardized' test specimens. Ball-on-flat wear tests in simulation of oral function are used to quantify susceptibility to protracted sliding contact damage. Wear rates for this class of dental material tend to increase with quasistatic parameter values, so the latter do not provide a reliable guide to longevity. The generation of severe-wear facets involves cumulative quasiplastic deformation and microcrack coalescence at the grain level. It is implied that interplay between wear and fracture mechanisms should be an important consideration in future microstructural design of dental ceramics, especially in the quest to balance durability against esthetics.
PMCID:7156428
PMID: 32279844
ISSN: 1878-0180
CID: 4392502
An in situ and ex situ study of the microstructural evolution of a novel lithium silicate glass-ceramic during crystallization firing
OBJECTIVE:To elucidate the compositional and microstructural developments of a novel lithium silicate glass-ceramic during its crystallization cycle. METHODS:Blocks of a lithium silicate glass-ceramic (Obsidian®, Glidewell Laboratories) were cut into 1mm thick plates and polished to 1μm finish. Some of them were crystallized prior to polishing. Firstly, ex situ compositional and microstructural characterizations of both the pre- and post-crystallized samples were performed by wavelength dispersive X-ray fluorescence, field-emission scanning electron microscopy, and X-ray diffractometry. Secondly, the pre-crystallized samples were subjected to in situ compositional and microstructural characterizations under non-isothermal heating by simultaneous thermogravimetry/differential scanning calorimetry, X-ray thermo-diffractometry, and field-emission scanning electron thermo-microscopy. RESULTS:) nanocrystals precipitate from the glass matrix. SIGNIFICANCE/CONCLUSIONS:The identification of compositional and microstructural developments of Obsidian® indicates that, by controlling the firing conditions, it is possible to tailor its microstructure, which in turn could affect its mechanical and optical properties, and ultimately its clinical performance.
PMID: 32278481
ISSN: 1879-0097
CID: 4401612
Effect of finishing/polishing techniques and low temperature degradation on the surface topography, phase transformation and flexural strength of ultra-translucent ZrO2 ceramic
OBJECTIVE:ceramic. METHODS:300 (n=15/group) of conventional zirconia (Z: Ice Zirkon Transluzent) and ultra-translucent zirconia (UT: Prettau Anterior) bar-specimens were made and divided according to the "Finishing/Polishing" - (C - Control, B - diamond rubber polishers, P - adjusting with burs, PB - adjusting with burs+diamond polishers, PG - adjusting with burs+glaze), "Low temperature Degradation (LTD)" (with or without a treatment at 127°C, 1.7bar/24h). Then, a 3-point mini flexural test was performed in a universal testing machine (1mm/min, 500kgf load cell). SEM, EDS, XDR, AFM, optical profilometry and Weibull analysis were performed. Data were analyzed by 3-way ANOVA and Tukey's post-test (5%). RESULTS:had the lowest value. Monoclinic phases were observed only in the conventional zirconia groups and were more evident after LTD. Diamond rubber polishers presented less roughness for both zirconias. SIGNIFICANCE/CONCLUSIONS:The use of diamond rubber polishers is the most suitable finishing/polishing method for zirconia ceramic restorations and that final glazing reduces the fracture resistance of these materials.
PMID: 32008750
ISSN: 1879-0097
CID: 4301052
An electroencephalographic signature predicts antidepressant response in major depression
Antidepressants are widely prescribed, but their efficacy relative to placebo is modest, in part because the clinical diagnosis of major depression encompasses biologically heterogeneous conditions. Here, we sought to identify a neurobiological signature of response to antidepressant treatment as compared to placebo. We designed a latent-space machine-learning algorithm tailored for resting-state electroencephalography (EEG) and applied it to data from the largest imaging-coupled, placebo-controlled antidepressant study (n = 309). Symptom improvement was robustly predicted in a manner both specific for the antidepressant sertraline (versus placebo) and generalizable across different study sites and EEG equipment. This sertraline-predictive EEG signature generalized to two depression samples, wherein it reflected general antidepressant medication responsivity and related differentially to a repetitive transcranial magnetic stimulation treatment outcome. Furthermore, we found that the sertraline resting-state EEG signature indexed prefrontal neural responsivity, as measured by concurrent transcranial magnetic stimulation and EEG. Our findings advance the neurobiological understanding of antidepressant treatment through an EEG-tailored computational model and provide a clinical avenue for personalized treatment of depression.
PMCID:7145761
PMID: 32042166
ISSN: 1546-1696
CID: 4400982
Edge chipping test in dentistry: A comprehensive review
OBJECTIVE:Literature on edge chipping test applied to dental materials and structures has been systematically reviewed with regard to the evaluation methods and parameters used. DATA/METHODS:A systematic search of the literature retrieved 3484 relevant studies. After removing duplicates, 1848 records were screened by titles and abstracts and 1797 were excluded; 51 papers were assessed full text for eligibility. Twenty papers were included in this study and they were organized according to the dental materials and structures tested as follows: 2 studies on human tooth, 9 on dental ceramics, 5 on polymer-based composites, and 4 studies evaluated both ceramic and polymer-based materials. SOURCES/METHODS:MEDLINE/PubMed, Scopus and Web of Science databases were searched up to June 2019 without restriction on date and language. STUDY SELECTION/METHODS:In vitro studies using edge chipping test on dental materials and structures were included. CONCLUSIONS:Different methods have been used for edge chipping test, regardless of reported parameters. There is significant evidence that edge chipping test is a relevant approach to predict chipping behavior of dental materials and tooth tissues because chips produced from most edge chipping studies are similar to clinically reported chipping failures.
PMID: 32001022
ISSN: 1879-0097
CID: 4294582
Sliding contact wear and subsurface damage of CAD/CAM materials against zirconia
OBJECTIVE:Most previous work conducted on the wear behavior of dental materials has focused on wear rates and surface damage. There is, however, scarce information regarding the subsurface damage arising from sliding contact fatigue. The aim of this study was to elucidate the wear mechanisms and the subsurface damage generated during sliding contact fatigue in 5 contemporary CAD/CAM materials against a zirconia indenter. METHODS:cycles, n=8). Analysis of the wear scars was conducted using light-microscopy, scanning-electron-microscopy and optical profilometry. Subsurface damage was assessed using sagittal and transverse sections of the samples. RESULTS:Fatigue wear mechanisms predominated in glassy materials (e.CAD, SUP, VMII), accompanied by extensive subsurface damage, whereas abrasive wear mechanisms were responsible for the large wear craters in the resin composite (LU) with an absolute absence of subsurface fracture. A combination of both mechanisms was observed in the polymer-infiltrated reinforced-glass (ENA), displaying large wear craters and severe subsurface damage. SIGNIFICANCE/CONCLUSIONS:Well-controlled laboratory simulation can identify wear and subsurface damage susceptibility of various classes of restorative materials. Both wear and subsurface fracture are determining factors for the long-term success of restorations.
PMID: 32007314
ISSN: 1879-0097
CID: 4301042
