I am preparing MDS Peridontology notes. I already have the textbook answer. Do NOT write a complete answer. Instead, provide only Landmark, highly cited, guideline-changing or examination-relevant research articles related to ROLE OF VITAMINS IN PERIODONTAL HEALTH AND DISEASE For each article, mention: Author, Year, Title, Journal, Study type (RCT, systematic review, clinical trial, guideline, etc.), Key contribution, why it is important for postgraduate exam. Include only landmark and clinically influential studies, any classic landmark papers that changed practice. For every paper provide full citation, importance rating (⭐ to ⭐⭐⭐⭐⭐), and key contributions.
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vitamin C periodontal disease
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vitamin D periodontal health supplementation
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vitamin E periodontal oxidative stress
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folic acid vitamin B periodontal gingival health
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Nishida vitamin C NHANES periodontal disease diet
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Nishida vitamin C NHANES periodontal smoking
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vitamin D VDR polymorphism bone loss periodontal alveolar
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Dietrich vitamin D serum 25-hydroxyvitamin D periodontal NHANES
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I now have comprehensive data for all the landmark papers. Let me compile a thorough, exam-ready reference list.
Landmark Research Articles: Role of Vitamins in Periodontal Health and Disease
For MDS Periodontology — Postgraduate Examination Reference
VITAMIN C (ASCORBIC ACID)
1. Nishida et al. (2000) - THE CLASSIC NHANES III STUDY ⭐⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Nishida M, Grossi SG, Dunford RG, Ho AW, Trevisan M, Genco RJ |
| Year | 2000 |
| Title | Dietary Vitamin C and the Risk for Periodontal Disease |
| Journal | Journal of Periodontology |
| PMID | 10972636 |
| DOI | 10.1902/jop.2000.71.8.1215 |
| Study Type | Cross-sectional, population-based (NHANES III) |
Key Contribution:
- Analyzed 12,419 adults from the US NHANES III database
- Found a dose-dependent, statistically significant relationship between reduced dietary vitamin C intake and increased risk of periodontal disease (OR = 1.19; 95% CI: 1.05-1.33)
- The relationship was strongest in current smokers (OR = 1.21) and former smokers (OR = 1.28)
- Dose-response: OR of 1.30 for those taking 0-29 mg/day vs. OR of 1.16 for 100-179 mg/day compared to ≥180 mg/day
Why It Is Important for PG Exams:
This is the most-cited population-level study establishing vitamin C as a dietary risk modifier for periodontal disease. It is cited in virtually every periodontal textbook including Carranza, Newman & Takei, and Lindhe. The use of NHANES III data, dose-response evidence, and the interaction with smoking make it a board-favorite. Genco RJ is a landmark author in periodontology.
2. Tada & Miura (2019) - SYSTEMATIC REVIEW OF VITAMIN C ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Tada A, Miura H |
| Year | 2019 |
| Title | The Relationship between Vitamin C and Periodontal Diseases: A Systematic Review |
| Journal | International Journal of Environmental Research and Public Health |
| PMID | 31336735 |
| DOI | 10.3390/ijerph16142472 |
| Study Type | Systematic Review (14 studies: 7 cross-sectional, 2 case-control, 2 cohort, 3 RCTs) |
Key Contribution:
- All 7 cross-sectional studies showed a negative association between vitamin C intake/blood levels and periodontal disease
- Case-control studies: periodontitis patients had lower vitamin C intake and blood levels than healthy controls
- RCT-level evidence: vitamin C improved gingival bleeding in gingivitis but did NOT improve outcomes in established periodontitis or alveolar bone loss
- Distinguishes the role of vitamin C in gingivitis prevention vs. periodontitis treatment
Why It Is Important for PG Exams:
First comprehensive systematic review dedicated to this topic. The critical exam point drawn from this paper is the distinction that vitamin C improves gingival inflammation but does not reverse periodontitis or regenerate alveolar bone - a classic exam discriminator.
3. Buzatu, Luca & Bumbu (2024) - META-ANALYSIS WITH POOLED OR ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Buzatu R, Luca MM, Bumbu BA |
| Year | 2024 |
| Title | Does Vitamin C Supplementation Provide a Protective Effect in Periodontal Health? A Systematic Review and Meta-Analysis |
| Journal | International Journal of Molecular Sciences |
| PMID | 39201285 |
| DOI | 10.3390/ijms25168598 |
| Study Type | Systematic Review and Meta-Analysis (16 studies, 17,853 participants) |
Key Contribution:
- Pooled OR = 1.52 (95% CI: 1.49-1.55) showing higher vitamin C intake significantly reduces periodontal disease risk
- High heterogeneity (I² = 95.46%) - reflects variability in study populations and designs
- Largest meta-analysis specifically on vitamin C supplementation and periodontal outcomes
- Reinforces that individual dietary needs and baseline vitamin C levels influence effectiveness - argues for personalized nutritional guidance
Why It Is Important for PG Exams:
Most current high-level evidence. The pooled OR and the concept of personalized nutritional guidance as part of comprehensive periodontal care is an emerging examination theme.
4. Abou Sulaiman & Shehadeh (2010) - RCT: VIT C AS ADJUNCT TO SRP ⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Abou Sulaiman AE, Shehadeh RMH |
| Year | 2010 |
| Title | Assessment of Total Antioxidant Capacity and the Use of Vitamin C in the Treatment of Non-Smokers with Chronic Periodontitis |
| Journal | Journal of Periodontology |
| PMID | 20569170 |
| DOI | 10.1902/jop.2010.100173 |
| Study Type | Randomized Controlled Trial (60 subjects, double-arm) |
Key Contribution:
- Plasma total antioxidant capacity (TAOC) was significantly lower in chronic periodontitis patients vs. healthy controls
- Non-surgical periodontal therapy (NSPT) alone improved TAOC and clinical parameters
- Adjunctive vitamin C did NOT offer additional benefit over SRP alone
- First RCT specifically examining TAOC as an outcome alongside clinical periodontal parameters
Why It Is Important for PG Exams:
A nuanced exam finding: while vitamin C deficiency is associated with periodontal disease, supplemental vitamin C as an adjunct to SRP does not give additional clinical benefit. This is a classic MCQ trap question and a frequently tested concept in MDS exams.
VITAMIN D
5. Dietrich et al. (2004) - LANDMARK NHANES III STUDY FOR VITAMIN D ⭐⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Dietrich T, Joshipura KJ, Dawson-Hughes B, Bischoff-Ferrari HA |
| Year | 2004 |
| Title | Association between Serum Concentrations of 25-Hydroxyvitamin D₃ and Periodontal Disease in the US Population |
| Journal | American Journal of Clinical Nutrition |
| PMID | 15213036 |
| DOI | 10.1093/ajcn/80.1.108 |
| Study Type | Cross-sectional population study (NHANES III), 11,202 subjects |
Key Contribution:
- Low serum 25(OH)D₃ was significantly and inversely associated with clinical attachment loss in subjects aged ≥50 years
- Men in lowest 25(OH)D quintile had 0.39 mm greater CAL; women had 0.26 mm greater CAL vs. highest quintile
- The effect was independent of bone mineral density (BMD) - suggesting a direct immunomodulatory mechanism beyond bone density effects
- No significant association found in adults under 50
Why It Is Important for PG Exams:
The definitive population-level study for vitamin D and periodontal disease. The independence from BMD effect (suggesting immunomodulation not just bone metabolism) is a highly testable examination point. Frequently cited as the paradigm-shift paper for vitamin D in periodontology.
6. Dietrich et al. (2005) - VITAMIN D AND GINGIVAL INFLAMMATION ⭐⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Dietrich T, Nunn M, Dawson-Hughes B, Bischoff-Ferrari HA |
| Year | 2005 |
| Title | Association between Serum Concentrations of 25-Hydroxyvitamin D and Gingival Inflammation |
| Journal | American Journal of Clinical Nutrition |
| PMID | 16155270 |
| DOI | 10.1093/ajcn.82.3.575 |
| Study Type | Cross-sectional (NHANES III, 6,700 never-smokers, 77,503 gingival units) |
Key Contribution:
- Sites in subjects in the highest 25(OH)D quintile were 20% less likely to bleed on probing (BOP) vs. lowest quintile (OR = 0.80; 95% CI: 0.69-0.92; P for trend <0.001)
- The association was linear across the entire 25(OH)D range, consistent across racial groups and sexes
- Proposed the anti-inflammatory mechanism of vitamin D as the primary driver (not just bone effects)
- Used never-smokers only to eliminate smoking confounding - methodological strength
Why It Is Important for PG Exams:
This is the seminal paper demonstrating vitamin D's anti-inflammatory role in the periodontium independent of bone effects. The 20% reduction in BOP figure is a board-examination staple. The "anti-inflammatory" mechanism concept is central to current periodontal immunopathology teaching.
7. Krall, Wehler, Garcia et al. (2001) - RCT: CALCIUM + VITAMIN D AND TOOTH LOSS ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Krall EA, Wehler C, Garcia RI, Harris SS, Dawson-Hughes B |
| Year | 2001 |
| Title | Calcium and Vitamin D Supplements Reduce Tooth Loss in the Elderly |
| Journal | American Journal of Medicine |
| PMID | 11690570 |
| DOI | 10.1016/S0002-9343(01)00899-3 |
| Study Type | Randomized Controlled Trial (145 subjects, aged ≥65 years, 3-year trial + 2-year follow-up) |
Key Contribution:
- Only 13% of the supplement group lost ≥1 tooth vs. 27% of the placebo group (OR = 0.4; 95% CI: 0.2-0.9) over the trial period
- Subjects with total calcium ≥1000 mg/day had lower tooth loss during the 2-year follow-up (40% vs. 59%; OR = 0.5)
- First RCT to demonstrate that calcium + vitamin D supplementation doses targeting osteoporosis prevention also improve tooth retention
- Made the bone-periodontal-systemic triangle clinically actionable
Why It Is Important for PG Exams:
The only well-designed RCT demonstrating that oral supplementation reduces tooth loss. The cross-link between osteoporosis management and periodontal/tooth retention is a highly popular exam topic, especially in the context of host modulation therapy.
8. Machado, Lobo, Proença et al. (2020) - SYSTEMATIC REVIEW + META-ANALYSIS ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Machado V, Lobo S, Proença L, Mendes JJ, Botelho J |
| Year | 2020 |
| Title | Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis |
| Journal | Nutrients |
| PMID | 32708032 |
| DOI | 10.3390/nu12082177 |
| Study Type | Systematic Review + Meta-Analysis (16 studies: 14 case-control, 2 intervention) |
Key Contribution:
- Pooled MD = -6.80 ng/mL (95% CI: -10.59 to -3.02) for serum 25(OH)D levels - periodontitis patients had significantly lower vitamin D vs. healthy controls
- Salivary 25(OH)D levels showed no significant difference between groups (important negative finding)
- Evidence insufficient to conclude benefit of vitamin D supplementation post-NSPT (only 2 intervention studies available)
- SORT A (strong) recommendation for the association between low 25(OH)D and periodontitis
Why It Is Important for PG Exams:
Best available pooled evidence summary. The SORT A recommendation and the specific mean difference (-6.80 ng/mL) are frequently cited in exam answers. The salivary vs. serum vitamin D distinction is a classic examination differentiator.
9. Liang et al. (2023) - UPDATED META-ANALYSIS: VIT D + SRP ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Liang F, Zhou Y, Zhang Z, Zhang Z, Shen J |
| Year | 2023 |
| Title | Association of Vitamin D in Individuals with Periodontitis: An Updated Systematic Review and Meta-Analysis |
| Journal | BMC Oral Health |
| PMID | 37312090 |
| DOI | 10.1186/s12903-023-03120-w |
| Study Type | Systematic Review + Meta-Analysis (16 articles including RCTs) |
Key Contribution:
- Serum vitamin D significantly lower in periodontitis (SMD = -0.88; 95% CI: -1.75 to -0.01)
- SRP + vitamin D significantly improved CAL compared to SRP alone (WMD = -0.13 mm, 95% CI: -0.19 to -0.06; P<0.01)
- SRP + vitamin D did NOT significantly improve probing depth, gingival index, or bleeding index vs. SRP alone
- Most current evidence supporting vitamin D supplementation as an adjunct to NSPT
Why It Is Important for PG Exams:
The most current and exam-relevant finding: adjunctive vitamin D improves CAL but not probing depth - a discriminating clinical detail. The role of vitamin D as a host modulation agent is a priority topic in the 2023 EFP classification-era curriculum.
COMBINED MULTI-VITAMIN / ANTIOXIDANT STUDIES
10. Varela-López et al. (2018) - COMPREHENSIVE SYSTEMATIC REVIEW: ALL VITAMINS ⭐⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Varela-López A, Navarro-Hortal MD, Giampieri F, Bullón P, Battino M, Quiles JL |
| Year | 2018 |
| Title | Nutraceuticals in Periodontal Health: A Systematic Review on the Role of Vitamins in Periodontal Health Maintenance |
| Journal | Molecules |
| PMID | 29783781 |
| DOI | 10.3390/molecules23051226 |
| Study Type | Systematic Review (human and animal studies, PubMed until Feb 2018) |
Key Contribution:
- Most complete systematic review covering ALL vitamins (A, B-complex, C, D, E, K) in periodontal health
- Concluded that vitamins with antioxidant capacity + immune effects (esp. vitamin C) and those involved in bone metabolism (esp. vitamin D) are most relevant to periodontal disease
- Identified vitamin C as most studied; vitamin D as having the most relevant role in bone metabolism
- Covered both preventive and therapeutic roles; included animal models alongside human data
Why It Is Important for PG Exams:
The go-to reference article for MDS written and viva examinations when asked about the holistic role of vitamins in periodontology. Covers all vitamins under one paper. The hierarchy (Vit C for antioxidant/immune, Vit D for bone) is a core exam answer framework.
11. Mi et al. (2024) - META-ANALYSIS: ALL 5 VITAMINS ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Mi N, Zhang M, Ying Z, Lin X, Jin Y |
| Year | 2024 |
| Title | Vitamin Intake and Periodontal Disease: A Meta-Analysis of Observational Studies |
| Journal | BMC Oral Health |
| PMID | 38245765 |
| DOI | 10.1186/s12903-024-03850-5 |
| Study Type | Meta-Analysis (23 studies, 74,488 participants, 45 effect groups) |
Key Contribution:
- All five vitamins (A, B-complex, C, D, E) showed a significant negative association with periodontal disease at higher intake levels:
- Vitamin A: OR 0.788 (95% CI: 0.640-0.971)
- Vitamin B complex: OR 0.884 (95% CI: 0.824-0.948)
- Vitamin C: OR 0.875 (95% CI: 0.775-0.988)
- Vitamin D: OR 0.964 (95% CI: 0.948-0.981)
- Vitamin E: OR 0.868 (95% CI: 0.776-0.971)
- Largest meta-analysis covering multiple vitamins simultaneously; robust sensitivity analysis
Why It Is Important for PG Exams:
This paper provides one table of ORs for all vitamins - an exam-ready data set. The finding that ALL five vitamins are protective is a unifying conclusion for theory papers and viva questions. Vitamin A's role (often underemphasized) is bolstered by this paper.
12. Muniz et al. (2015) - ANTIOXIDANTS + PERIODONTAL THERAPY (Lycopene, Vit C, Vit E) ⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Muniz FW, Nogueira SB, Mendes FL, Rösing CK, et al. |
| Year | 2015 |
| Title | The Impact of Antioxidant Agents Complimentary to Periodontal Therapy on Oxidative Stress and Periodontal Outcomes: A Systematic Review |
| Journal | Archives of Oral Biology |
| PMID | 26067357 |
| DOI | 10.1016/j.archoralbio.2015.05.007 |
| Study Type | Systematic Review (only RCTs: double-blind or blind) |
Key Contribution:
- Reviewed lycopene, vitamin C, vitamin E, fruit/vegetable capsules, and dietary interventions as adjuncts to periodontal therapy
- Only lycopene and vitamin E showed statistically significant improvement in periodontal clinical parameters vs. control
- Vitamin C as adjunct did NOT significantly improve clinical outcomes beyond periodontal therapy alone
- Oxidative stress outcomes did not uniformly improve with antioxidant supplementation
Why It Is Important for PG Exams:
Demonstrates the nuanced difference between vitamins: vitamin E shows clinical benefit as an adjunct whereas vitamin C alone does not. The role of lycopene (a carotenoid antioxidant) emerging as a local adjunct is a novel topic. Frequently tested in host modulation therapy questions.
FOLIC ACID (VITAMIN B9)
13. Pack & Thomson (1980) - CLASSIC FOLATE RCT IN PREGNANCY ⭐⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Pack AR, Thomson ME |
| Year | 1980 |
| Title | Effects of Topical and Systemic Folic Acid Supplementation on Gingivitis in Pregnancy |
| Journal | Journal of Clinical Periodontology |
| PMID | 7007454 |
| DOI | 10.1111/j.1600-051x.1980.tb02013.x |
| Study Type | Double-blind Randomized Controlled Trial (30 pregnant women) |
Key Contribution:
- Topical folate mouthwash produced a highly significant improvement in gingival health during the 8th month of pregnancy (p<0.001), despite no change in plaque index
- Systemic folate (5 mg tablets) did NOT significantly improve gingival inflammation
- Demonstrated that local/topical folate absorption through gingival tissues has a direct gingival protective effect
- Showed folate's role in pregnancy gingivitis - a specific clinical entity
Why It Is Important for PG Exams:
This is the foundational paper on folate in periodontal disease. The topical > systemic effect is a classic exam question. The context of pregnancy gingivitis + folate deficiency as a modifying factor is highly testable. Folate rinse reducing BOP without reducing plaque is a classic question about host modulation vs. plaque control.
14. Keceli et al. (2020) - FOLIC ACID ADJUNCT TO SRP, CRP, HOMOCYSTEINE ⭐⭐⭐
| Field | Details |
|---|---|
| Authors | Keceli HG, Ercan N, Karsiyaka Hendek M |
| Year | 2020 |
| Title | The Effect of Systemic Folic Acid Intake as an Adjunct to Scaling and Root Planing on Clinical Parameters and Homocysteine and C-Reactive Protein Levels in GCF of Periodontitis Patients: A Randomized Placebo-Controlled Clinical Trial |
| Journal | Journal of Clinical Periodontology |
| PMID | 32109317 |
| Study Type | Randomized Placebo-Controlled Clinical Trial |
Key Contribution:
- Systemic folic acid as an adjunct to SRP reduced homocysteine levels and CRP in GCF - linking folate to systemic inflammatory markers
- Adds the periodontal-cardiovascular disease link dimension: elevated homocysteine (reduced by folate) is a cardiovascular risk factor
- Demonstrated that SRP + folic acid may benefit not just local periodontium but also systemic inflammatory burden
Why It Is Important for PG Exams:
Connects folate to the periodontal-systemic link via homocysteine, which is a cutting-edge examination topic. The GCF CRP reduction as a surrogate for systemic inflammation is a testable concept in the era of the 2018 EFP/AAP classification.
CHAPPLE et al. - GUIDELINE-LEVEL CONSENSUS ⭐⭐⭐⭐⭐
15. Chapple et al. (2017) - EFP/ORCA WORKSHOP CONSENSUS STATEMENT
| Field | Details |
|---|---|
| Authors | Chapple ILC, Bouchard P, Cagetti MG, et al. |
| Year | 2017 |
| Title | Interaction of Lifestyle, Behaviour or Systemic Diseases with Dental Caries and Periodontal Diseases: Consensus Report of Group 2 of the Joint EFP/ORCA Workshop |
| Journal | Journal of Clinical Periodontology |
| PMID | 28266114 |
| Study Type | Consensus Statement / Systematic Review / Practice Guideline |
Key Contribution:
- Official European Federation of Periodontology (EFP) position on nutritional and lifestyle factors in periodontal disease
- Formally recognized diet and nutritional status (including vitamins) as modifying risk factors for periodontal diseases
- Placed vitamin C, vitamin D, and antioxidant status within the framework of lifestyle risk factors for periodontitis
- Guideline-level endorsement for dietary counseling as part of periodontal care
Why It Is Important for PG Exams:
This is a practice guideline paper from EFP - the most authoritative European periodontal body. Any statement from Chapple (who is the 2018 EFP/AAP classification lead author) carries enormous exam weight. Citing this paper places the role of vitamins within the official 2017 EFP framework - essential for MDS theory answers.
QUICK EXAM-REFERENCE TABLE
| Vitamin | Landmark Paper | Year | Key Exam Point |
|---|---|---|---|
| C | Nishida et al. (NHANES III) | 2000 | Dose-response; strongest effect in smokers; OR = 1.19 |
| C | Tada & Miura SR | 2019 | Improves gingivitis BOP; does NOT reverse periodontitis or bone loss |
| C | Abou Sulaiman RCT | 2010 | Adjunctive vit C does NOT improve SRP outcomes - classic trap |
| D | Dietrich et al. (NHANES III) | 2004 | Low 25(OH)D → higher CAL; independent of BMD; aged ≥50 |
| D | Dietrich et al. (Gingival) | 2005 | 20% less BOP at highest 25(OH)D quintile; anti-inflammatory mechanism |
| D | Krall et al. RCT | 2001 | Ca + vit D → 60% less tooth loss; only RCT for tooth retention |
| D | Machado et al. SR+MA | 2020 | Pooled MD = -6.80 ng/mL; serum NOT salivary levels differ |
| D | Liang et al. MA | 2023 | SRP + vit D improves CAL but not PPD |
| Multi | Varela-López et al. SR | 2018 | All vitamins covered; C for antioxidant, D for bone - exam framework |
| Multi | Mi et al. MA | 2024 | All 5 vitamins (A,B,C,D,E) show negative association; largest dataset (74,488) |
| E | Muniz et al. SR | 2015 | Only vit E + lycopene improve clinical parameters as adjuncts; not vit C |
| B9/Folate | Pack & Thomson RCT | 1980 | Topical folate rinse reduces BOP in pregnancy; systemic does NOT |
| B9/Folate | Keceli et al. RCT | 2020 | Folic acid + SRP reduces GCF homocysteine + CRP (systemic link) |
| EFP | Chapple et al. Consensus | 2017 | Official guideline placing vitamins as lifestyle modifying factors |
TOP 5 MUST-KNOW FOR VIVA AND THEORY
- Nishida 2000 - The NHANES III vitamin C study (dose-response, OR, smoking interaction)
- Dietrich 2004 + 2005 - The two NHANES III vitamin D papers (bone-independent, anti-inflammatory, 20% BOP reduction)
- Varela-López 2018 - The comprehensive systematic review covering all vitamins
- Krall 2001 - Only RCT showing calcium + vit D reduces actual tooth loss
- Pack & Thomson 1980 - Classic topical folate in pregnancy gingivitis (topical > systemic)
Note: For "Nishida et al. 2000 - Calcium and the risk for periodontal disease" (J Periodontol 2000;71:1057-66) - a companion paper from the same group analyzing calcium intake from NHANES III data also exists and is frequently cited alongside the vitamin C paper. Include it if your faculty syllabus covers mineral-vitamin interplay.
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