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Nevin Manimala Statistics

Association of PM2.5 Exposure and Alzheimer Disease Pathology in Brain Bank Donors-Effect Modification by APOE Genotype

Neurology. 2024 Mar 12;102(5):e209162. doi: 10.1212/WNL.0000000000209162. Epub 2024 Feb 21.

ABSTRACT

BACKGROUND AND OBJECTIVES: Fine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The APOE gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM2.5 and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort.

METHODS: A cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC) score. Traffic-related PM2.5 concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250 m. One-year, 3-year, and 5-year average PM2.5 concentrations before death were matched to participants’ home address. We assessed the association between traffic-related PM2.5 and AD hallmark pathology and effect modification by APOE genotype, using adjusted ordinal logistic regression models.

RESULTS: Among the 224 participants, the mean age of death was 76 years, and 57% had at least 1 APOE ε4 copy. Traffic-related PM2.5 was significantly associated with the CERAD score for the 1-year exposure window (odds ratio [OR] 1.92; 95% CI 1.12-3.30) and the 3-year exposure window (OR 1.87; 95% CI 1.01-3.17). PM2.5 was also associated with higher Braak stage and ABC score albeit nonsignificantly. The strongest associations between PM2.5 and neuropathology markers were among those without APOE ε4 alleles (e.g., for the CERAD score and 1-year exposure window, OR 2.31; 95% CI 1.36-3.94), though interaction between PM2.5 and APOE genotype was not statistically significant.

DISCUSSION: Our study found traffic-related PM2.5 exposure was associated with the CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM2.5 affects β-amyloid deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this association.

PMID:38382009 | DOI:10.1212/WNL.0000000000209162

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Long-Term Longitudinal Course of Cognitive and Motor Symptoms in Patients With Cerebral Small Vessel Disease

Neurology. 2024 Mar 12;102(5):e209148. doi: 10.1212/WNL.0000000000209148. Epub 2024 Feb 21.

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients with cerebral small vessel disease (SVD) show a heterogenous clinical course. The aim of the current study was to investigate the longitudinal course of cognitive and motor function in patients who developed parkinsonism, dementia, both, or none.

METHODS: Participants were from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study, a prospective cohort of patients with SVD. Parkinsonism and dementia were, respectively, diagnosed according to the UK Parkinson’s Disease Society brain bank criteria and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for major neurocognitive disorder. Linear and generalized linear mixed-effect analyses were used to study the longitudinal course of motor and cognitive tasks.

RESULTS: After a median follow-up of 12.8 years (interquartile range 10.2-15.3), 132 of 501 (26.3%) participants developed parkinsonism, dementia, or both. Years before diagnosis of these disorders, participants showed distinct clinical trajectories from those who developed none: Participant who developed parkinsonism had an annual percentage of 22% (95% CI 18%-27%) increase in motor part of the Unified Parkinson’s Disease Rating Scale score. This was significantly higher than the 16% (95% CI 14%-18%) of controls, mainly because of a steep increase in bradykinesia and posture and gait disturbances. When they developed dementia as well, the increase in Timed Up and Go Test time of 0.73 seconds per year (95% CI 0.58-0.87) was significantly higher than the 0.20 seconds per year increase (95% CI 0.16-0.23) of controls. All groups, including the participants who developed parkinsonism without dementia, showed a faster decline in executive function compared with controls: Annual decline in Z-score was -0.07 (95% CI -0.10 to -0.05), -0.09 (95% CI -0.11 to -0.08), and -0.11 (95% CI -0.14 to -0.08) for participants who developed, respectively, parkinsonism, dementia, and both parkinsonism and dementia. These declines were all significantly faster than the annual decline in Z-score of 0.07 (95% CI -0.10 to -0.05) of controls.

DISCUSSION: A distinct pattern in deterioration of clinical markers is visible in patients with SVD, years before the diagnosis of parkinsonism and dementia. This knowledge aids early identification of patients with a high risk of developing these disorders.

PMID:38382000 | DOI:10.1212/WNL.0000000000209148

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Effect of Aging on the Mechanical Properties of CAD/CAM-Milled and 3D-Printed Acrylic Resins for Denture Bases

Int J Prosthodont. 2024 Feb 21;37(7):1-7. doi: 10.11607/ijp.8376.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the mechanical properties of acrylic resins at different aging times for denture bases manufactured using the conventional method, microwave processing, milling, and 3D printing.

MATERIALS AND METHODS: A total of 160 rectangular samples (64 Å~ 10 Å~ 3.3 ± 0.03 mm) were prepared, divided among the four main resin groups, and subdivided into four analysis times (T0, T1, T2, and T3), resulting in 10 samples per subgroup. The samples were stored in distilled water at 37° ± 2°C for 24 hours (T0), then subjected to thermocycling at temperatures of 5° ± 1°C and 55° ± 1°C in different numbers of cycles: 5,000 (T1); 10,000 (T2); and 20,000 (T3). The mechanical properties evaluated were surface microhardness, flexural strength, and modulus of elasticity. Statistical differences between resin groups and aging time were evaluated using two-way analysis of variance (P < .05).

RESULTS: The 3D-printed resin showed the significantly lowest values of microhardness, flexural strength, and modulus of elasticity compared to other resins (P < .001).

CONCLUSIONS: The CAD/CAM-milled denture resin showed mechanical properties similar to those of traditional resins (conventional and microwave-processed). The 3D-printing resin did not show adequate mechanical properties for long-term clinical use. Despite this, new studies are developing better properties of this resin for long-term use.

PMID:38381998 | DOI:10.11607/ijp.8376

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Receipt of Guideline-Concordant Care Is Associated With Improved Survival in Patients With Osteosarcoma in California: A Population-Based Analysis

JCO Oncol Pract. 2024 Feb 21:OP2300591. doi: 10.1200/OP.23.00591. Online ahead of print.

ABSTRACT

PURPOSE: To examine the relationship between guideline-concordant care (GCC) on the basis of national clinical practice guidelines and survival in children (0-14 years), adolescents and young adults (AYAs, 15-39 years), and adults (40 years and older) with osteosarcoma, and to identify sociodemographic and clinical factors associated with receipt of GCC and survival.

METHODS: We used data from the California Cancer Registry (CCR) on patients diagnosed with osteosarcoma during 2004-2019, with detailed treatment information extracted from the CCR text fields, including chemotherapy regimens. Multivariable logistic and Cox proportional hazard regression were used for statistical analyses.

RESULTS: Of 1,716 patients, only 47% received GCC, with variation by age at diagnosis: 67% of children, 43% of AYAs, and 30% of adults. In multivariable models, patients who received part or all care (v none) at specialized cancer centers were more likely to receive GCC. AYAs and adults were less likely to receive GCC than children (odds ratio [OR], 0.38 [95% CI, 0.30 to 0.50] and OR, 0.40 [95% CI, 0.28 to 0.56], respectively). In a model excluding adults, patients treated by pediatric (v medical) oncologists were more likely to receive GCC (OR, 3.44 [95% CI, 2.40 to 4.94]). Patients with metastatic osteosarcoma at diagnosis who did not receive GCC had a greater hazard of death (hazard ratio [HR], 2.02 [95% CI, 1.55 to 2.63]) but no statistical differences were found in those diagnosed at earlier stages (HR, 1.15 [95% CI, 0.92 to 1.43]).

CONCLUSION: GCC was associated with improved survival in patients with metastatic osteosarcoma in California. However, we found disparities in the delivery of GCC, highlighting the need for target interventions to improve delivery of GCC in this patient population.

PMID:38381995 | DOI:10.1200/OP.23.00591

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US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer

J Clin Oncol. 2024 Feb 21:JCO2302112. doi: 10.1200/JCO.23.02112. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).

PATIENTS AND METHODS: Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2- advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator’s choice of ET (n = 239).

RESULTS: In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia.

CONCLUSION: The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

PMID:38381994 | DOI:10.1200/JCO.23.02112

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Marginal Fit and Internal Adaptation of Monolithic Zirconia 3-Unit Fixed Dental Prosthesis: In Vitro Study

Int J Prosthodont. 2024 Feb 21;37(1):109. doi: 10.11607/ijp.8087.

ABSTRACT

PURPOSE: To compare the marginal and internal fit of monolithic zirconia (MZ) 3-unit fixed dental prostheses (FDPs) fabricated using two CAD/CAM workflows: full-chairside (FCH) and lab (LAB).

MATERIALS AND METHODS: The right maxillary first premolar and first molar were prepared for MZ 3-unit FDPs on a typodont. CEREC Primescan digitized the typodont model 15 Omes. A total of 30 FDPs was fabricated using two processes: FCH (n = 15) and LAB (n = 15). FCH and LAB FDPs were designed using CEREC SW 4.5.1 and Exocad and milled using CEREC MC X and Zirkonzhan 600/V3, respectively. A fast-sintering protocol was used in both groups. A dual-scan technique was used to assess the cement space at the occlusal surface (OC), axial wall (AX), and margin (MA). Statistical analysis of the results was performed using univariate ANOVA with Scheff. post hoc test (a = .05).

RESULTS: Measurements in the FCH and LAB groups were within the clinically acceptable marginal and internal fit. The fit of FCH FDPs at MA, AX, and OC was 77.50 ± 29.99 μm, 99.67 ± 21.58 μm, and 150.03 ± 30.78 μm, respectively. The fit of LAB FDPs at MA, AX, and OC was 100.27 ± 27.06 μm, 116.53 ± 17.90 μm, and 142.30 ± 19.00 μm, respectively. The difference between the two groups was not statistically significant.

CONCLUSIONS: MZ 3-unit FDPs fabricated using FCH have clinically acceptable marginal and internal fit. This result verifies the ability of FCH workflow to fabricate MZ mulOunit FDPs in a single visit.

PMID:38381993 | DOI:10.11607/ijp.8087

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Influence of Immediate Dentin Sealing on Marginal Gaps of Laminate Veneers: Machinable Monolithic Zirconia Versus Pressable Lithium Dislocate. An In Vitro Study

Int J Prosthodont. 2024 Feb 21;37(1):109. doi: 10.11607/ijp.8008.

ABSTRACT

PURPOSE: To investigate the influence of immediate dentin sealing (IDS) vs delayed dentin sealing (DDS) on the marginal gaps of machinable monolithic zirconia (MMZ) vs pressable lithium disilicate (PLD) laminate veneers.

MATERIALS AND METHODS: A total of 40 maxillary lateral incisors were used and received butt-joint laminate veneer preparation. The samples were divided into two groups (n = 20 each) according to ceramic material: PLD ceramic was used in the first group, and MMZ was used in the second. Each group was then divided into two subgroups according to the bonding protocol: IDS was employed in one, and DDS in the other (n = 10 each). The marginal gap widths were measured using digital microscopy and statistically analyzed.

RESULTS: The smallest marginal gaps were observed in MMZ-DDS (57.2 ± 8.4 μm), followed by PLD-DDS (62.4 ± 2.7 μm) and MMZ-IDS (63.5 ± 1.9 μm). The largest marginal gaps were observed in PLD-IDS (81.5 ± 6.3 μm). Two-way ANOVA revealed that the bonding technique (P < .001) and ceramic material (P < .001) both showed significant differences.

CONCLUSIONS: MMZ produced beIer marginal accuracy than PLD. IDS seems to have a predisposition to significantly wider marginal gaps than DDS, but these gaps are within the clinically acceptable range. The marginal accuracy of ceramic veneers appears to be related to the bonding technique as well as the material of construction.

PMID:38381991 | DOI:10.11607/ijp.8008

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Accuracy of Silicone Impressions and Stone Models Using Two Laboratory Scanners: A 3D Evaluation

Int J Prosthodont. 2024 Feb 21;37(1):109. doi: 10.11607/ijp.8074.

ABSTRACT

PURPOSE: To evaluate the in vitro accuracy of impressions obtained with two silicone and corresponding stone models using two laboratory scanners.

MATERIALS AND METHODS: A master model with synthetic resin teeth with two single-unit crown preparations was created and scanned using a 12-megapixel scanner. Five conventional impressions of the physical model were prepared with different silicone impression systems (Zhermack and Coltene) using the double-mix technique and poured with gypsum. The impressions and stone models obtained were scanned using two extraoral scanning systems (Identica T500, Medit; S600 ARTI, Zirkonzahn). All best-fit superimpositions of the teeth areas were conducted between the master model and the scans of the impressions and models obtained with the two scanners. A P < .05 level was considered significant.

RESULTS: The Identica T500 Medit scanner showed an accuracy of 102.34 (89.67, 115.01) μm for Coltene silicone and 79.51 (67.82, 91.21) μm for Zhermack silicone, while the S600 ARTI Zirkonzhan scanner presented 110.79 (98.24, 123.33) μm and 91.91 (81.29, 102.54) μm, respectively, with significant differences between scanners for Zhermack silicone (P = .008) and for the corresponding stone models (P = .002). Zhermack silicone presented overall discrepancies lower than Coltene silicone, with statistically significant differences in both scanners analyzed (P < .001; P = .017). However, the discrepancies found were within clinically acceptable values. With the Zirkonzahn scanner, discrepancies found in the Zhermack impressions were lower than in the corresponding stone models (P < .001).

CONCLUSIONS: The direct digitization of silicone impressions with laboratory scanners presented comparable results to conventional techniques with stone models.

PMID:38381990 | DOI:10.11607/ijp.8074

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Frequency of Contamination on Used Healing Abutments after Sterilization: An In Vitro Study

Int J Prosthodont. 2024 Feb 21;37(1):109.

ABSTRACT

PURPOSE: To determine and compare the frequency of contamination on different sites of healing abutments (HAs) after sterilization with Phloxine B dye on unused and used HAs after sterilization.

MATERIALS AND METHODS: A total of 60 HAs were divided into two test groups: (1) used and sterilized and (2) a control group (unused). The test group was evaluated for contamination after sterilization; the control group did not undergo any procedure. Data were analyzed using SPSS version 22 (IBM). Descriptive statistics were used to determine the frequency of contamination in the different groups and at the different HA sites. Chi-square test was used to evaluate the association of frequency of contamination with the HA site and design. The level of significance was kept at P ≤ .01.

RESULTS: The test group showed more contamination compared to the control group. The most contaminated sites were the screw thread and the screwdriver engagement location.

CONCLUSIONS: HA reuse is cost-effective, but cleaning and sterilization was not effective for these components; thus, HAs need to be reused with caution because they were heavily contaminated when compared to new HAs. Among the different sites, the screw thread and screwdriver engagement sites were more prone to contamination. HA type did not influence the frequency of contamination.

PMID:38381989

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Mechanical Properties of Zirconia Materials with Different Translucency: An In Vitro Study

Int J Prosthodont. 2024 Feb 21;37(1):72-79. doi: 10.11607/ijp.8164.

ABSTRACT

PURPOSE: To investigate the biaxial flexural strength of zirconia materials with different translucency before and after aging procedures and to evaluate the effects of aging on hardness and surface characteristics.

MATERIALS AND METHODS: A total of 90 disc-shaped specimens (n = 30 each) were prepared from translucent (Upcera-ST, Upcera Dental), high translucent (Katana HT, Kuraray Noritake), and ultra high translucent (Katana UTML, Kuraray Noritake) zirconia materials to a ø.16 ±1.2 mm thickness. The different translucency discs were then divided into three subgroups; one group was subjected to aging in a chewing simulator (n = 10), one group was aged with thermocycling (n = 10), and one was a control group (n = 10). Biaxial flexural strength, Vickers hardness, and surface characteristics were examined for all discs. The data were analyzed using the Shapiro-Wilk (P = .05), Mann-Whitney U, and Kruskal-Wallis H tests. Fracture strength was determined using biaxial bending strength tests, and Weibull analysis was used to analyze the resulting data.

RESULTS: A statistically significant difference was found among zirconia materials with different translucency in terms of fracture strength. On average, fracture strength was highest in the Upcera ST group (1,932.87 MPa) and lowest in the Katana UTML group (1,073.6 MPa; P = .001). The results of Weibull analysis showed a statistically similar distribution for all groups.

CONCLUSIONS: Aging procedures did not cause significant differences in fracture strength and hardness. The fracture strength of the zirconia materials with different translucency was considered acceptable for intraoral use.

PMID:38381986 | DOI:10.11607/ijp.8164