197 results on '"Lalla E"'
Search Results
52. Oral disease burden in Northern Manhattan patients with diabetes mellitus.
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Lalla E, Park DB, Papapanou PN, and Lamster IB
- Abstract
OBJECTIVES: We explored the association between diabetes mellitus and oral disease in a low-socioeconomic-status urban population. METHODS: Dental records of 150 adults with diabetes and 150 nondiabetic controls from the dental clinic at Columbia University in Northern Manhattan matched by age and gender were studied. RESULTS: There was a 50% increase in alveolar bone loss in diabetic patients compared with nondiabetic controls. Diabetes, increasing age, male gender, and use of tobacco products had a statistically significant effect on bone loss. CONCLUSIONS: Our findings provide evidence that diabetes is an added risk for oral disease in this low-income, underserved population of Northern Manhattan. Oral disease prevention and treatment programs may need to be part of the standards of continuing care for patients with diabetes. [ABSTRACT FROM AUTHOR]
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- 2008
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53. Accelerated tooth eruption in children with diabetes mellitus.
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Lal S, Cheng B, Kaplan S, Softness B, Greenberg E, Goland RS, Lalla E, and Lamster IB
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- 2008
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54. Analytical database of Martian minerals (ADaMM): Project synopsis and Raman data overview
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Jesus Saiz, Emmanuel Lalla, Aurelio Sanz-Arranz, Luis Miguel Nieto, Jesús Medina, Clara Garcia-Prieto, Elena Pascual-Sánchez, Guillermo Lopez-Reyes, Andoni Moral, Marco Veneranda, Fernando Rull, Jose Antonio Manrique, Menelaos Konstantinidis, Veneranda, M. [0000-0002-7185-2791], Lalla, E. A. [0000-0002-0005-1006], Moral, A. G. [0000-0002-6190-8560], López Reyes, G. [0000-0003-1005-1760], Agencia Estatal de Investigación (AEI), and European Commission (EC)
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Martian ,010504 meteorology & atmospheric sciences ,Mars 2020 ,25 Ciencias de la Tierra y del Espacio ,01 natural sciences ,ExoMars ,Astrobiology ,symbols.namesake ,Mineral database ,0103 physical sciences ,symbols ,General Materials Science ,22 Física ,Spectroscopy ,Raman spectroscopy ,010303 astronomy & astrophysics ,Raman ,Geology ,0105 earth and related environmental sciences - Abstract
Producción Científica, The Mars2020/Perseverance and ExoMars/Rosalind Franklin rovers are bothslated to return the first Raman spectra ever collected from another planetarysurface, Mars. In order to optimize the rovers scientific outcome, the scientificcommunity needs to be provided with tailored tools for data treatment andinterpretation. Responding to this need, the purpose of the Analytical Databaseof Martian Minerals (ADaMM) project is to build an extended multianalyticaldatabase of mineral phases that have been detected on Mars or are expected tobe found at the landing sites where the two rovers will operate. Besides the useof conventional spectrometers, the main objective of the ADaMM database isto provide access to data collected by means of laboratory prototypes simulat-ing the analytical performances of the spectroscopic systems onboard the Mars2020 and ExoMars rovers. Planned to be released to the public in 2022,ADaMM will also provide access to data treatment and visualization toolsdeveloped in the framework of the mentioned space exploration missions. Assuch, the present work seeks to provide an overview of the ADaMM onlineplatform, spectral tools, and mineral collection. In addition to that, themanuscript describes the Raman spectrometers used to analyze the mineralcollection and presents a representative example of the analytical performanceensured by the Raman prototypes assembled to simulate the Raman LaserSpectrometer (RLS) and SuperCam systems., European Union’s Horizon 2020 research and innovation program. grant agreement no. 687302., Ministerio de Economía y Competitividad (Grant/Award Number: PID2019-107442RB-C31)
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- 2021
55. Raman characterization of terrestrial analogs from the AMADEE‐18 astronaut simulated mission using the ExoMars RLS simulator: Implications for Mars
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Emmanuel Lalla, Jorge L. Vago, Gernot Groemer, Jose Antonio Manrique, Menelaos Konstantinidis, Fernando Rull, Michael Daly, Marco Veneranda, Guillermo Lopez-Reyes, López Reyes, G. [0000-0003-1005-1760], Veneranda, M. [0000-0002-7185-2791], Daly, M. [0000-0002-3733-2530], Lalla, E. A. [0000-0002-0005-1006], Konstantinidis, M. [0000-0002-5074-9023], Manrique, J. A. [0000-0002-2053-2819], Unidad de Excelencia Científica María de Maeztu Centro de Astrobiología del Instituto Nacional de Técnica Aeroespacial y CSIC, MDM-2017-0737, Ministerio de Economía y Competitividad (MINECO), and Agencia Estatal de Investigación (AEI)
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Engineering ,business.industry ,Steering committee ,media_common.quotation_subject ,Simulated missions ,Library science ,Mars Exploration Program ,010502 geochemistry & geophysics ,Exploration of Mars ,Mars exploration ,Mineralogy ,7. Clean energy ,01 natural sciences ,ExoMars ,13. Climate action ,Excellence ,0103 physical sciences ,Martian analog ,General Materials Science ,business ,010303 astronomy & astrophysics ,Spectroscopy ,0105 earth and related environmental sciences ,Planetary exploration ,media_common - Abstract
This work is funded by the Spanish Ministerio de Economía y Competitividad (MINECO) under references ESP2014‐56138‐C3‐2‐R and ESP2107‐87690‐C3‐1‐R. We would like to thank The Austrian Space Forum (OeWF) and the AMADEE‐18 Oman National Steering Committee, in particular, Dr. Saleh Al‐Shidhani and the government and people of the Sultanate of Oman. The Planetary Exploration Instrumentation Laboratory (PIL) at York University is especially thankful for the financial support provided by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Ontario Centre of Excellence (OCE), and the Canadian Space Agency. E. A. Lalla would like to express gratitude to the Ontario Centre of Excellence (OCE) for the TalentEdge Postdoctoral Funding during the development of the present manuscript. The authors are grateful to Dr. K. Tait and V. Di Cecco for the opportunity to carry out measurements at the Royal Ontario Museum (ROM) and their excellent support., Between February 1 and February 28, 2018, the Austrian Space Forum, in cooperation with research teams from 25 nations, conducted the AMADEE-18 mission—a human-robotic Mars expedition simulation in the Dhofar region in the Sultanate of Oman. As a part of the AMADEE-18 simulated Mars human exploration mission, the Remote Science Support team investigated the Dhofar area (Oman) to qualify it as a potential Mars analog site. The motivation of this research was to study and register selected samples collected by the analog astronauts during the AMADEE-18 mission with the European Space Agency (ESA) ExoMars Raman Laser Spectrometer (RLS) simulator, compare the results with standard laboratory measurements, and establish the implication of the results to the future ESA ExoMars mission. The Raman measurements identified minerals such as carbonates (calcite and dolomite), feldspar and plagioclase (albite, anorthite, orthoclase, and sanidine), Fe-oxides (goethite, hematite, and magnetite), and Ti-oxide (anatase), each relevant to planetary exploration. As we have presented here, Raman spectroscopy is a powerful tool for detecting the presence of organic molecules, particularly by analyzing the principal vibration of C-C and C-H bonds. It has also been shown that portable Raman spectroscopy is a relevant tool for in situ field studies such as those conducted during extra-vehicular activities (EVA) in simulated missions like the AMADEE-18 and the future AMADEE-2020 campaign., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737) ; Spanish Ministerio de Economía y Competitividad (MINECO) under references ESP2014‐56138‐C3‐2‐R and ESP2107‐87690‐C3‐1‐R
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- 2020
56. Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions
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Jasim M. Albandar, Carlo Ercoli, Kazuhisa Yamazaki, Korkud Demirel, Evanthia Lalla, Pierpaolo Cortellini, Michael P. Mills, Michael K. McGuire, Lijian Jin, Søren Jepsen, Anton Sculean, Philip M. Preshaw, Nicola X West, Francis J. Hughes, Jack G. Caton, Nicolaas C. Geurs, Mark A. Reynolds, Phoebus N. Madianos, Cristiano Susin, Philippe Bouchard, Debora C Matthews, Jingyuan Fan, Nabil F. Bissada, Massimo de Sanctis, Alpdogan Kantarci, Jepsen, S., Caton, J. G., Albandar, J. M., Bissada, N. F., Bouchard, P., Cortellini, P., Demirel, K., de Sanctis, M., Ercoli, C., Fan, J., Geurs, N. C., Hughes, F. J., Jin, L., Kantarci, A., Lalla, E., Madianos, P. N., Matthews, D., Mcguire, M. K., Mills, M. P., Preshaw, P. M., Reynolds, M. A., Sculean, A., Susin, C., West, N. X., Yamazaki, K., Jepsen, Søren, Caton, Jack G., Albandar, Jasim M., Bissada, Nabil F., Bouchard, Philippe, Cortellini, Pierpaolo, Demirel, Korkud, de Sanctis, Massimo, Ercoli, Carlo, Fan, Jingyuan, Geurs, Nicolaas C., Hughes, Francis J., Jin, Lijian, Kantarci, Alpdogan, Lalla, Evanthia, Madianos, Phoebus N., Matthews, Debora, Mcguire, Michael K., Mills, Michael P., Preshaw, Philip M., Reynolds, Mark A., Sculean, Anton, Susin, Cristiano, West, Nicola X., and Yamazaki, Kazuhisa
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0301 basic medicine ,gingival inflammation ,diagnosis ,gingival thickness ,Peri ,Junctional epithelium ,periodontal disease ,Dentistry ,systemic disease ,Esthetics, Dental ,Gingivitis ,0302 clinical medicine ,periodontiti ,dental restorations ,tooth ,610 Medicine & health ,gingiviti ,dental prostheses ,gingival recession ,diagnosi ,classification ,mucogingival surgery ,Periodontics ,medicine.symptom ,Occlusal trauma ,attachment loss ,medicine.medical_specialty ,anatomy ,Consensus ,Dental Plaque ,Dental plaque ,03 medical and health sciences ,genetic disease ,medicine ,plastic periodontal surgery ,Humans ,dental prosthese ,gingival thickne ,Workgroup ,attachment lo ,Intensive care medicine ,Periodontitis ,Gingival recession ,Periodontal Diseases ,bruxism ,dental restoration ,business.industry ,occlusal trauma ,030206 dentistry ,Periodontium ,medicine.disease ,Peri-Implantitis ,stomatognathic diseases ,030104 developmental biology ,Clinical attachment loss ,Implant ,business - Abstract
Background: A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly prevalent and often associated with hypersensitivity, the development of caries and non-carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations. Methods: Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants. Results: Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon-Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm-induced inflammation (such as neoplastic diseases); 2) diabetes-associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking – now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues – is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non-carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm-induced gingival inflammation and loss of periodontal supporting tissues. Conclusion: An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented.
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- 2018
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57. Results of the COLDWATER randomized controlled trial: enhanced performance of underwater cold snare polypectomy for colorectal polyps 5-10 mm, independent of endoscopist experience.
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Zachou M, Nifora M, Androutsakos T, Katsaras G, Varytimiadis K, Zoumpouli C, Karantanos P, Lalla E, Mpetsios G, Panoutsakou M, Stoica R, Thermou D, Mavrogenis G, Ntikoudi E, Nikiteas N, Sougioultzis S, Kalaitzakis E, and Kykalos S
- Abstract
Background: The wide range of R0 resection rates (R0RR) and incomplete resection rates (IRR) observed with conventional cold snare polypectomy (CCSP) emphasizes the necessity for technique enhancement. The COLDWATER study aimed to compare underwater cold snare polypectomy (UCSP) to CCSP for 5-10-mm colorectal polyps, focusing on comprehensive histopathological evaluation, efficacy, and safety., Methods: This was a randomized, single-blind, controlled trial comparing UCSP to CCSP for non-pedunculated colorectal polyps of size 5-10 mm. The primary outcome was to report differences in the muscularis mucosa resection ratio. The secondary outcomes focused on differences in depth of excision, R0-RR, IRR, en bloc resection rate, adverse events, and recurrence rate., Results: The COLDWATER study found higher muscularis mucosa resection in UCSP (81.72±62.81% vs. CCSP: 72.33±22.33%, P=0.003) with comparable submucosa presence (UCSP: 16.6%, CCSP: 12.5%, P=0.25). UCSP showed better outcomes regarding IRR (3.5% vs. 8.5%, P=0.05) and en bloc resection (98% vs. 93.5%, P=0.04). In CCSP, expert endoscopists achieved higher R0RR than non-experts, while UCSP showed no significant difference in R0RR across endoscopist's experience levels., Conclusions: UCSP achieves a more extensive excision of the muscularis mucosa compared to CCSP, even though it does not attain a deeper excision. Additionally, UCSP shows a higher en bloc resection rate, with lower rates of IRR, and emerges as a promising technique for training inexperienced endoscopists in polypectomy, given its experience-independent success in achieving R0 resection., Competing Interests: Conflict of Interest: None, (Copyright: © 2024 Hellenic Society of Gastroenterology.)
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- 2024
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58. Postmenopausal women with HIV have increased tooth loss.
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Wadhwa S, Finn TR, Kister K, Matsumura S, Levit M, Cantos A, Shah J, Bohn B, Lalla E, Grbic JT, Demmer RT, and Yin MT
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- Middle Aged, Humans, Female, Aged, Postmenopause, Aging, Alveolar Process, Tooth Loss, Periodontal Diseases
- Abstract
Background: With effective antiretroviral therapy, people with HIV (PWH) are living longer and aging; the majority of PWH in the United States are now over the age of 50 and in women have gone through the menopause transition. Menopause potentiates skeletal bone loss at the spine, hip, and radius in PWH. The alveolar bone which surronds the teeth is different than long bones because it is derived from the neural crest. However, few studies have assessed the oral health and alveolar bone in middle aged and older women with HIV. Therefore, the objective of this study was to evaluate periodontal disease and alveolar bone microarchitecture in postmenopausal women with HIV., Methods: 135 self-reported postmenopausal women were recruited (59 HIV-, 76 HIV + on combination antiretroviral therapy with virological suppression) from a single academic center. The following parameters were measured: cytokine levels (IFN-γ, TNF-α, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17 A, OPG, and RANKL) in gingival crevicular fluid, bleeding on probing, probing depth, clinical attachment loss, number of teeth present, alveolar crestal height, and alveolar bone microarchitecture., Results: The mean age of participants was 57.04+/-6.25 years and a greater proportion of women with HIV were black/African American (HIV + 68.42%, HIV- 23.73%; p < 0.001). There was no significant difference in bleeding on probing (p = 0.17) and attachment loss (p = 0.39) between women who were HIV infected vs. HIV uninfected. Women with HIV had significantly higher RANKL expression in Gingival Crevicular Fluid (HIV + 3.80+/-3.19 pg/ul, HIV- 1.29+/-2.14 pg/ul ; p < 0.001), fewer teeth present (HIV + 17.75+/-7.62, HIV- 22.79+/-5.70; p < 0.001), ), lower trabecular number (HIV + 0.08+/-0.01, HIV- 0.09+/-0.02; p = 0.004) and greater trabecular separation (HIV + 9.23+/-3.11, HIV- 7.99+/-3.23; p = 0.04) compared to women without HIV that remained significant in multivariate logistic regression analysis in a sub-cohort after adjusting for age, race/ethnicity, smoking status, and diabetes., Conclusion: Postmenopausal women with HIV have deterioration of the alveolar trabecular bone microarchitecture that may contribute to greater tooth loss., (© 2023. The Author(s).)
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- 2024
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59. Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.
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Agiannitopoulos K, Pepe G, Tsaousis GN, Potska K, Bouzarelou D, Katseli A, Ntogka C, Meintani A, Tsoulos N, Giassas S, Venizelos V, Markopoulos C, Iosifidou R, Karageorgopoulou S, Christodoulou C, Natsiopoulos I, Papazisis K, Vasilaki-Antonatou M, Kabletsas E, Psyrri A, Ziogas D, Lalla E, Koumarianou A, Anastasakou K, Papadimitriou C, Ozmen V, Tansan S, Kaban K, Ozatli T, Eniu DT, Chiorean A, Blidaru A, Rinsma M, Papadopoulou E, and Nasioulas G
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- Female, Humans, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing methods, Exons, Genetic Testing, DNA Copy Number Variations, Ovarian Neoplasms genetics
- Abstract
Background/aim: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice., Materials and Methods: A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA)., Results: Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants., Conclusion: In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2023
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60. Post-polypectomy coagulation syndrome: a tricky to diagnose hot snare problem that can be eliminated thanks to cold snare revolution.
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Zachou M, Pikramenos K, Mpetsios G, Lalla E, Panoutsakou M, Varytimiadis K, and Karantanos P
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Post-polypectomy syndrome or post-polypectomy coagulation syndrome (PPCS) is a rare adverse event of thermal injury caused during hot snare aided, endoscopic mucosal resection of colon polyps. Its diagnosis is tricky as it is commonly misdiagnosed as perforation leading to unnecessary exploratory abdominal surgeries. The authors aim to present an early diagnosed and successfully treated, case of PPCS, and to highlight the difference in the safety profile of two techniques; hot snare versus cold snare polypectomy.
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- 2022
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61. Infliximab (IFX)-Biosimilar Induced Drug-Induced Liver Injury (DILI): A Case Report.
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Zachou M, Pikramenos K, Panoutsakou M, Lalla E, and Androutsakos T
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Infliximab (IFX) is a chimeric human-murine monoclonal antibody that prevents tumor necrosis factor alpha (TNF-α) activation by binding to both soluble and transmembrane forms of TNF-α. Antagonists of TNF (anti-TNF agents) can cause drug-induced liver injury (DILI). We present a non-anti-TNF naïve patient suffering from severe Crohn's disease who developed DILI with a hepatocellular pattern, without jaundice, after two infusions of an IFX biosimilar., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Zachou et al.)
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- 2022
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62. Prognostic Significance of Low HER2 Expression in Patients With Metastatic Hormone Receptor-positive Breast Cancer Treated With First Line CDK4/6 Inhibitors: A Greek Multicenter Real-world Data Analysis.
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Douganiotis G, Kesisis G, Lalla E, Korantzis I, Boukovinas I, and Papazisis K
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Background/aim: Low expression of HER2 has defined a new "HER2-low" subgroup of breast cancer with distinct clinicopathological characteristics and both prognostic and predictive implications. The impact of low HER2 expression in metastatic hormone receptor-positive HER2-negative breast cancer treated with first-line CDK4/6 inhibitors has not been studied. Using real-world patient data, we aimed to identify prognostic differences in this patient population according to HER2 expression with immunohistochemistry., Patients and Methods: We retrospectively analyzed 191 patients from 5 Oncology Department databases in Thessaloniki, Greece, with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in the first line, for whom detailed immunohistochemical HER2 data could be retrieved., Results: Median progression-free survival was numerically different among the different HER2 subgroups (3.35 years for HER2 0 tumors, 2.18 years for HER2 +1 tumors, 1.74 years for HER2 +2/ISH-negative tumors), but this difference was not statistically significant (p=0.477). Median PFS was statistically significantly longer in patients without visceral metastases (5.45 years) compared to patients with visceral metastases (1.61 years) (p=0.017). Median PFS was also statistically significantly longer in patients taking an aromatase inhibitor (2.99 years) compared to patients taking fulvestrant (1.33 years) (p<0.0001). There were no statistically significant differences in the other subgroups examined., Conclusion: CDK4/6 inhibitors are equally effective as first-line treatment agents, regardless of the exact level of HER2 expression. Numerical differences, however, do exist among the different HER2 subgroups, and merit further evaluation in future studies to better study this phenomenon., Competing Interests: GD declares no relevant conflict of interest. GK has received honoraria and consultancy fees from Amgen, Avaviosis, Astellas, AstraZeneca, Boehringer, BMS, Demo, Galenica, Ipsen, LEO Pharma, Merck, MSD, Novartis, Pfizer, Roche, and Sanofi. EL has received honoraria and consultancy fees from AstraZeneca, Genesis Pharma, Novartis, Pfizer, Roche, and Amgen. IK has received honoraria and consultancy fees from Boehringer, Sandoz, Amgen, Roche, AstraZeneca, Pfizer, Novartis, Sanofi, MSD, Merck and BMS. IB has received honoraria and consultancy fees from Sandoz, Amgen, Roche, AstraZeneca, Ipsen, Pfizer, Novartis, Sanofi, Genesis Pharma, MSD, LEO pharma, Merck, Servier and BMS and Research Funding from Boehringer, Regeneron, Eli Lilly, Pfizer, Novartis, BMS, MSD and Roche. KP has received honoraria and consultancy fees from MSD, Gilead, AstraZeneca, Novartis, Eli Lilly, Roche and GSK and Research Funding from Roche, Novartis, Daiichi Sankyo, Eli Lilly, AstraZeneca, BMS, Boehringer and EISAI., (Copyright 2022, International Institute of Anticancer Research.)
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- 2022
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63. Spectroscopic study of terrestrial analogues to support rover missions to Mars - A Raman-centred review.
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Rull F, Veneranda M, Manrique-Martinez JA, Sanz-Arranz A, Saiz J, Medina J, Moral A, Perez C, Seoane L, Lalla E, Charro E, Lopez JM, Nieto LM, and Lopez-Reyes G
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- Extraterrestrial Environment chemistry, Spectrum Analysis, Raman methods, Mars, Space Flight
- Abstract
The 2020s could be called, with little doubt, the "Mars decade". No other period in space exploration history has experienced such interest in placing orbiters, rovers and landers on the Red Planet. In 2021 alone, the Emirates' first Mars Mission (the Hope orbiter), the Chinese Tianwen-1 mission (orbiter, lander and rover), and NASA's Mars 2020 Perseverance rover reached Mars. The ExoMars mission Rosalind Franklin rover is scheduled for launch in 2022. Beyond that, several other missions are proposed or under development. Among these, MMX to Phobos and the very important Mars Sample Return can be cited. One of the key mission objectives of the Mars 2020 and ExoMars 2022 missions is the detection of traces of potential past or present life. This detection relies to a great extent on the analytical results provided by complementary spectroscopic techniques. The development of these novel instruments has been carried out in step with the analytical study of terrestrial analogue sites and materials, which serve to test the scientific capabilities of spectroscopic prototypes while providing crucial information to better understand the geological processes that could have occurred on Mars. Being directly involved in the development of three of the first Raman spectrometers to be validated for space exploration missions (Mars 2020/SuperCam, ExoMars/RLS and RAX/MMX), the present review summarizes some of the most relevant spectroscopy-based analyses of terrestrial analogues carried out over the past two decades. Therefore, the present work describes the analytical results gathered from the study of some of the most distinctive terrestrial analogues of Martian geological contexts, as well as the lessons learned mainly from ExoMars mission simulations conducted at representative analogue sites. Learning from the experience gained in the described studies, a general overview of the scientific outcome expected from the spectroscopic system developed for current and forthcoming planetary missions is provided., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2022
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64. Decoding the role of macrophages in periodontitis and type 2 diabetes using single-cell RNA-sequencing.
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Agrafioti P, Morin-Baxter J, Tanagala KKK, Dubey S, Sims P, Lalla E, and Momen-Heravi F
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- Aged, Biomarkers metabolism, Bone Marrow metabolism, Cell Lineage genetics, Female, Gingiva metabolism, Humans, Inflammation genetics, Inflammation metabolism, Lipopolysaccharide Receptors genetics, Male, Middle Aged, Monocytes metabolism, Myeloid Cells metabolism, Sequence Analysis, RNA methods, Signal Transduction genetics, Transcription Factors genetics, Transcription, Genetic genetics, Transcriptome genetics, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Macrophages metabolism, Periodontitis genetics, Periodontitis metabolism, RNA genetics
- Abstract
Macrophages are resident myeloid cells in the gingival tissue which control homeostasis and play a pivotal role in orchestrating the immune response in periodontitis. Cell heterogeneity and functional phenotypes of macrophage subpopulations in periodontitis remain elusive. Here, we isolated gingival tissue from periodontitis-affected and healthy sites of patients with and without type 2 diabetes mellitus (T2DM). We then used single-cell RNA-sequencing (scRNA-seq) to define the heterogeneity of tissue-resident macrophages in gingival tissue in health vs. periodontitis. scRNA-seq demonstrated an unforeseen gene expression heterogeneity among macrophages in periodontitis and showed transcriptional and signaling heterogeneity of identified subsets in an independent cohort of patients with periodontitis and T2DM. Our bioinformatic inferences indicated divergent expression profiles in macrophages driven by transcriptional regulators CIITA, RELA, RFX5, and RUNX2. Macrophages in periodontitis expressed both pro-inflammatory and anti-inflammatory markers and their polarization was not mutually exclusive. The majority of macrophages in periodontitis expressed the monocyte lineage marker CD14, indicating their bone marrow lineage. We also found high expression and activation of RELA, a subunit of the NF-κB transcription factor complex, in gingival macrophages of periodontitis patients with T2DM. Our data suggested that heterogeneity and hyperinflammatory activation of macrophages may be relevant to the pathogenesis and outcomes of periodontitis, and may be further augmented in patients with T2DM., (© 2022 Federation of American Societies for Experimental Biology.)
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- 2022
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65. ExoMars Raman Laser Spectrometer: A Tool to Semiquantify the Serpentinization Degree of Olivine-Rich Rocks on Mars.
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Veneranda M, Lopez-Reyes G, Pascual Sanchez E, Krzesińska AM, Manrique-Martinez JA, Sanz-Arranz A, Lantz C, Lalla E, Moral A, Medina J, Poulet F, Dypvik H, Werner SC, Vago JL, and Rull F
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- Extraterrestrial Environment, Iron Compounds, Lasers, Magnesium Compounds, Silicates, Exobiology, Mars
- Abstract
We evaluated the effectiveness of the ExoMars Raman laser spectrometer (RLS) to determine the degree of serpentinization of olivine-rich units on Mars. We selected terrestrial analogs of martian ultramafic rocks from the Leka Ophiolite Complex (LOC) and analyzed them with both laboratory and flight-like analytical instruments. We first studied the mineralogical composition of the samples (mostly olivine and serpentine) with state-of-the-art diffractometric (X-ray diffractometry [XRD]) and spectroscopic (Raman, near-infrared spectroscopy [NIR]) laboratory systems. We compared these results with those obtained using our RLS ExoMars Simulator. Our work shows that the RLS ExoMars Simulator successfully identified all major phases. Moreover, when emulating the automatic operating mode of the flight instrument, the RLS ExoMars Simulator also detected several minor compounds (pyroxene and brucite), some of which were not observed by NIR and XRD ( e.g ., calcite). Thereafter, we produced RLS-dedicated calibration curves ( R
2 between 0.9993 and 0.9995 with an uncertainty between ±3.0% and ±5.2% with a confidence interval of 95%) to estimate the relative content of olivine and serpentine in the samples. Our results show that RLS can be very effective in identifying serpentine, a scientific target of primary importance for the potential detection of biosignatures on Mars-the main objective of the ExoMars rover mission.- Published
- 2021
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66. The impact of smoking on non-surgical periodontal therapy: A systematic review and meta-analysis.
- Author
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Chang J, Meng HW, Lalla E, and Lee CT
- Subjects
- Dental Scaling, Humans, Periodontal Attachment Loss therapy, Root Planing, Smokers, Smoking adverse effects, Chronic Periodontitis therapy
- Abstract
Aim: Smoking is a risk factor for periodontitis. This study aimed to evaluate the impact of smoking on clinical outcomes of non-surgical periodontal therapy., Materials and Methods: Electronic databases were searched to screen studies published before May 2020. The included studies had to have two groups: smokers (S) and non-smokers (NS) with periodontitis. The outcomes evaluated were differences between groups in probing depth (PD) reduction and clinical attachment level (CAL) gain after non-surgical periodontal therapy. Meta-regressions were conducted to evaluate correlations between outcomes and other contributing factors., Results: Seventeen studies were included. The post-treatment PD reduction in the S group was smaller than in the NS group (weighted mean difference in PD reduction: -0.33 mm, 95% confidence interval (CI): [-0.49, -0.17], p < .01). The CAL gain in the S group was also smaller than in the NS group (weighted mean difference in CAL gain: -0.20 mm, CI: [-0.39, -0.02], p < .01). Additionally, baseline PD significantly affected the difference in PD reduction between two groups., Conclusions: Smoking negatively impacts clinical responses to non-surgical periodontal therapy. Smokers with periodontitis have significantly less PD reduction and CAL gain than non-smokers., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
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67. ExoMars Raman Laser Spectrometer (RLS): development of chemometric tools to classify ultramafic igneous rocks on Mars.
- Author
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Veneranda M, Lopez-Reyes G, Manrique-Martinez JA, Sanz-Arranz A, Lalla E, Konstantinidis M, Moral A, Medina J, and Rull F
- Abstract
This work aims to evaluate whether the multi-point analysis the ExoMars Raman Laser Spectrometer (RLS) will perform on powdered samples could serve to classify ultramafic rocks on Mars. To do so, the RLS ExoMars Simulator was used to study terrestrial analogues of Martian peridotites and pyroxenites by applying the operational constraints of the Raman spectrometer onboard the Rosalind Franklin rover. Besides qualitative analysis, RLS-dedicated calibration curves have been built to estimate the relative content of olivine and pyroxenes in the samples. These semi-quantitative results, combined with a rough estimate of the concentration ratio between clino- and ortho-pyroxene mineral phases, were used to classify the terrestrial analogues. XRD data were finally employed as reference to validate Raman results. As this preliminary work suggests, ultramafic rocks on Mars could be effectively classified through the chemometric analysis of RLS data sets. After optimization, the proposed chemometric tools could be applied to the study of the volcanic geological areas detected at the ExoMars landing site (Oxia Planum), whose mineralogical composition and geological evolution have not been fully understood.
- Published
- 2020
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68. Immediate versus delayed temporization at posterior single implant sites: A randomized controlled trial.
- Author
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Wang J, Lerman G, Bittner N, Fan W, Lalla E, and Papapanou PN
- Subjects
- Bicuspid surgery, Crowns, Dental Implantation, Endosseous, Dental Prosthesis, Implant-Supported, Follow-Up Studies, Humans, Tooth Socket surgery, Treatment Outcome, Alveolar Bone Loss, Dental Implants, Single-Tooth, Immediate Dental Implant Loading
- Abstract
Aims: We conducted a randomized controlled trial to assess the clinical outcomes of two loading protocols involving either immediate or delayed prosthetic temporization of single implants placed at posterior, healed sites., Materials and Methods: Forty-nine patients in need of single implants at premolar or molar sites were randomized to receive a temporary crown either immediately after implant placement or 3 months later. Randomization was stratified by sex, implant location (premolar/molar) and arch (maxilla/mandible). Final implant screw-retained zirconia crowns with angulated screw channels were delivered at 5 months after surgery. Radiographic bone levels (primary outcome), peri-implant mucosal margin levels and peri-implant probing depths were recorded at baseline, 6 and 12 months after surgery., Results: Both treatment arms showed similar patterns of soft tissue and bone re-modelling from the implant platform over 12 months [mean bone level change 1.6 mm (SD 1.0 mm) in the delayed, and 1.2 mm (SD 1.3 mm) in the immediate temporization group], with the majority of changes occurring within the first 6 months., Conclusions: Immediate or delayed temporization of single implants placed at posterior healed sites resulted in largely similar 1-year outcomes with respect to peri-implant bone levels and soft tissue changes., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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69. Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group.
- Author
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Fountzilas E, Koliou GA, Vozikis A, Rapti V, Nikolakopoulos A, Boutis A, Christopoulou A, Kontogiorgos I, Karageorgopoulou S, Lalla E, Tryfonopoulos D, Boukovinas I, Rapti C, Nikolaidi A, Karteri S, Moirogiorgou E, Binas I, Mauri D, Aravantinos G, Zagouri F, Saridaki Z, Psyrri A, Bafaloukos D, Koumarianou A, Res E, Linardou H, Mountzios G, Razis E, Fountzilas G, and Koumakis G
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Endocrine System, Female, Humans, Middle Aged, Prospective Studies, Retrospective Studies, Breast Neoplasms drug therapy
- Abstract
Background: We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi)., Patients and Methods: We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs., Results: From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events., Conclusions: Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs., Trial Registration Number: NCT04133207., Competing Interests: Competing interests: EF: stock ownership: GENPREX INC, ARIAD and Deciphera Pharmaceuticals, Inc. Travel grant: Merck, Pfizer and K.A.M Oncology/Hematology. Advisory: LEO Pharma. Speaker fees: Roche and Pfizer. AV: advisory boards: Angelini and Takeda. Speaker fees: Bristol-Myers Squibb, Roche and MSD. Training programmes: Astellas, Genesis Pharma, Pfizer, LEO, Abbvie and TEVAAN. Travel fees: Pfizer, Merck, Hospira, Sanofi, Roche, Astra Zeneca, Kyowa Kirin-Anabiosis and Rafarm. AB: advisory role and honorarium: Pfizer and Novartis. SK: consultation/advisory: Astra Zeneca and Roche. Research: Novartis and Roche. Speaker: Astra Zeneca, Novartis and Roche. IB: advisory board: Pfizer and Novartis. Educational grant: Pfizer. Research Fund: Novartis and Lilly. AN: advisory board and speaker fees: Pfizer and Novartis. GA: advisory boards: Novartis, BMS, Roche Hellas, Astra Zeneca, Sanofi, Amgen, Genesis Pharma, Merck and Pfizer. AP: consultation fees: Amgen, Merck Serono, Roche, BMS, Astra Zeneca and MSD. Honoraria: Amgen, Merck Serono, Roche, BMS, Astra Zeneca and MSD. Research funds: BMS and Kura. AK: advisory role: Genesis Pharma. Honoraria: Pfizer. Speaker’s bureau: Roche. Research funding: Merck. Travel: MSD. Educational grants: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis and Ipsen. GM: honoraria/consultancy: Astra Zeneca, Roche, Pfizer, BMS, MSD, Takeda, Boehringer, Merck, Novartis and Amgen. Travel fees: Astra Zeneca, Roche, Pfizer, BMS, MSD, Takeda, Boehringer, Merck, Novartis, Astellas and Pierre Fabre. ER: consulting or advisory role: Astra Zeneca, Bristol-Myers Squibb and Pfizer. Research funding: Novartis, Demo Pharmaceutical, EORTC, Radius Pharmaceuticals, Tesaro, Parexel and Anabiosis Pharmaceuticals. Travel: Sanofi, Ipsen, Genesis Pharmaceuticals, LEO Pharma, Merck, Roche and Genekor. GF: advisory board: Pfizer, Sanofi and Roche. Honoraria: Astra Zeneca. Stock ownership: ARIAD and GENPREX. The rest of the authors declare no conflict of interest., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ on behalf of the European Society for Medical Oncology.)
- Published
- 2020
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70. Disruption of Monocyte and Macrophage Homeostasis in Periodontitis.
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Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, and Momen-Heravi F
- Subjects
- B7-H1 Antigen biosynthesis, B7-H1 Antigen genetics, CD47 Antigen biosynthesis, CD47 Antigen genetics, Cells, Cultured, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 immunology, GPI-Linked Proteins analysis, Gingiva immunology, Gingiva pathology, Gingival Hemorrhage etiology, HLA-DR Antigens biosynthesis, HLA-DR Antigens genetics, Homeostasis, Humans, Immunity, Innate, Inflammation, Lipopolysaccharide Receptors analysis, Macrophages classification, Macrophages metabolism, Monocytes metabolism, Periodontitis complications, Receptors, IgG analysis, Signal Transduction, Transcription Factors metabolism, Macrophages immunology, Monocytes immunology, Periodontitis immunology
- Abstract
Monocytes and macrophages are major cellular components of the innate immunity that play essential roles in tissue homeostasis. The contribution of different subsets of monocytes/macrophages to periodontal health and disease has not been fully elucidated. Type 2 diabetes mellitus (T2DM) is a risk factor for periodontitis. We hypothesized that the monocyte/macrophage signaling is perturbed in periodontitis-affected sites versus periodontally healthy sites and that this perturbation plays a critical role in the pathogenesis of periodontitis. Pairs of gingival tissue samples (each from a periodontally healthy and a periodontitis-affected site of the same patient) were harvested from 27 periodontitis patients, with and without T2DM. Each sample was processed to form a single-cell suspension, and a flow-cytometry panel was designed and validated to study monocyte and macrophage phenotypes. In separate experiments, the transcriptional changes associated with a pro-inflammatory phenotype were also examined in monocyte/macrophage subsets obtained from peripheral blood of patients with T2DM versus diabetes-free controls. A significantly higher proportion of intermediate (CD14
+ CD16+ ) monocytes was observed in periodontitis-affected tissues compared to healthy tissues. These monocytes overexpressed HLA-DR and PDL1 molecules, suggesting their activated inflammatory status. PDL1 increase was specific to intermediate monocytes. The ratio of M1/M2 macrophages was also significantly higher in periodontally affected sites, signifying an imbalance between inflammatory and repair mechanisms. We found a significantly higher expression of PDL1 in overall monocytes and M1 macrophages in periodontitis-affected sites compared to controls. Importantly, we identified a subpopulation of M1 macrophages present in periodontally affected tissues which expressed high levels of CD47, a glycoprotein of the immunoglobulin family that plays a critical role in self-recognition and impairment of phagocytosis. Analysis of the transcriptional landscape of monocytes/macrophages in gingival tissue of T2DM patients with periodontitis revealed a significant disruption in homeostasis toward a proinflammatory phenotype, elevation of pro-inflammatory transcription factors STAT1 and IRF1, and repression of anti-inflammatory JMJD3 in circulating monocytes. Taken together, our results demonstrate disruption of myeloid-derived cell homeostasis in periodontitis, with or without T2DM, and highlight a potentially significant role of these cell types in its pathogenesis. The impact of macrophage and monocyte signaling pathways on the pathobiology of periodontitis should be further evaluated., (Copyright © 2020 Almubarak, Tanagala, Papapanou, Lalla and Momen-Heravi.)- Published
- 2020
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71. Impact of connective tissue graft thickness on surgical outcomes: A pilot randomized clinical trial.
- Author
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Moisa DH, Connolly JA, Cheng B, and Lalla E
- Subjects
- Connective Tissue, Follow-Up Studies, Gingiva, Humans, Tooth Root, Treatment Outcome, Gingival Recession, Surgical Flaps
- Abstract
Background: The aim of this study was to compare thick versus thin connective tissue grafts (CTG) for the treatment of gingival recession, over a 3-month period., Methods: Forty-two CTG procedures were performed on single tooth Miller Class I or II recession defects at either premolar or anterior sites in 30 individuals. Procedures were randomized (1:1 ratio) to CTG thickness of 1 or 2 mm (parallel group design). Primary outcomes were the change in the width of the zone of keratinized tissue and the amount of root coverage achieved 3 months postoperatively at the recipient site. Secondary outcomes included change in the thickness of keratinized tissue at 3 months and patient-reported outcomes, such as pain, bleeding, and swelling at both the recipient and donor sites at 1 week, 2 weeks, 1 month, and 3 months., Results: No significant differences were found between the two groups for any of the primary or secondary outcomes. Mean root coverage achieved was 2.1 ± 0.2 mm in the 1-mm thick group and 2.5 ± 0.2 mm in the 2-mm thick group (P = 0.33). Keratinized tissue width was increased by 2.2 ± 0.2 mm in the 1-mm thick group and by 2.7 ± 0.3 mm in the 2-mm thick group (P = 0.18). Keratinized tissue thickness was increased by 1.0 ± 0.1 mm and by 1.2 ± 0.1 mm in the 1- and 2-mm thick groups, respectively (P = 0.09)., Conclusion: Within the current study limitations, our results suggest that similar root coverage and increase in the width and thickness of keratinized tissue can be achieved at 3 months whether a 1- or 2-mm thick CTG is used., (© 2019 American Academy of Periodontology.)
- Published
- 2019
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72. Soluble Forms of the Receptor for Advanced Glycation Endproducts (RAGE) in Periodontitis.
- Author
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Detzen L, Cheng B, Chen CY, Papapanou PN, and Lalla E
- Subjects
- Adult, Antigens, Neoplasm blood, Biomarkers blood, Body Mass Index, Female, Gingiva metabolism, Gingiva pathology, Humans, Inflammation blood, Inflammation pathology, Male, Middle Aged, Mitogen-Activated Protein Kinases blood, Periodontitis blood, Periodontitis pathology, Solubility, Antigens, Neoplasm genetics, Glycation End Products, Advanced genetics, Inflammation genetics, Mitogen-Activated Protein Kinases genetics, Periodontitis genetics
- Abstract
The receptor for advanced glycation endproducts (RAGE) is critically involved in the pathobiology of chronic inflammatory diseases. Soluble forms of RAGE have been proposed as biomarkers of severity in inflammatory and metabolic conditions, and in monitoring therapeutic responses. The aim of the present study was to determine circulating levels of the soluble forms of RAGE in periodontitis and to evaluate the expression of cell-bound, full-length RAGE and its antagonist AGER1 locally, in gingival tissues. Periodontitis patients and periodontally healthy, sex- and age-matched controls (50 per group) were included. Serum levels of total soluble RAGE and cleaved RAGE (cRAGE) were significantly lower in periodontitis patients. Levels of the endogenous secretory esRAGE were similar in the two groups. cRAGE remained significantly lower in the periodontitis group following multiple adjustments, and had a statistically significant inverse correlation with body mass index and all periodontal parameters. In periodontitis patients, gene expression of full-length RAGE and of AGER1 were significantly higher in periodontitis-affected gingival tissues compared to healthy gingiva. Soluble forms of RAGE, particularly cRAGE, may serve as biomarkers for the presence and severity/extent of periodontitis, and may be implicated in its pathogenesis and its role as a systemic inflammatory stressor.
- Published
- 2019
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73. Impact of diabetes on clinical periodontal outcomes following non-surgical periodontal therapy.
- Author
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Hsu YT, Nair M, Angelov N, Lalla E, and Lee CT
- Subjects
- Dental Scaling, Follow-Up Studies, Humans, Periodontal Attachment Loss, Root Planing, Chronic Periodontitis, Diabetes Mellitus
- Abstract
Aim: This systematic review aimed to evaluate the impact of diabetes mellitus on clinical outcomes of non-surgical periodontal therapy., Materials and Methods: Searches were conducted in electronic databases to screen studies published from January 1960 to August 2018. The included studies had at least two groups of patients: chronic periodontitis only (P) or both diabetes and chronic periodontitis (DMP). Outcomes of interest included the difference between the two groups in probing depth (PD) reduction and clinical attachment level (CAL) gain following non-surgical periodontal therapy. Meta-regression was conducted to evaluate the correlation between the outcomes of interest and contributing factors., Results: A total of 12 studies with a follow-up period up to 6 months were included. There was no significant difference in PD reduction (p = 0.55) or CAL gain (p = 0.65) between the two groups. A positive association between PD reduction and baseline PD difference (p = 0.03), and a negative association between PD reduction and age (p = 0.04) were found. The level of HbA1c at baseline did not significantly affect the difference in PD reduction (p = 0.39) or CAL gain (p = 0.44) between two groups., Conclusions: Recognizing the study's limitations, we conclude that diabetes mellitus (HbA1c ≤ 8.5%) does not appear to significantly affect short-term clinical periodontal outcomes of non-surgical periodontal treatment., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
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74. Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.
- Author
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Jepsen S, Caton JG, Albandar JM, Bissada NF, Bouchard P, Cortellini P, Demirel K, de Sanctis M, Ercoli C, Fan J, Geurs NC, Hughes FJ, Jin L, Kantarci A, Lalla E, Madianos PN, Matthews D, McGuire MK, Mills MP, Preshaw PM, Reynolds MA, Sculean A, Susin C, West NX, and Yamazaki K
- Subjects
- Consensus, Esthetics, Dental, Humans, Dental Plaque, Gingivitis, Periodontal Diseases, Periodontitis
- Abstract
Background: A variety of systemic diseases and conditions can affect the course of periodontitis or have a negative impact on the periodontal attachment apparatus. Gingival recessions are highly prevalent and often associated with hypersensitivity, the development of caries and non-carious cervical lesions on the exposed root surface and impaired esthetics. Occlusal forces can result in injury of teeth and periodontal attachment apparatus. Several developmental or acquired conditions associated with teeth or prostheses may predispose to diseases of the periodontium. The aim of this working group was to review and update the 1999 classification with regard to these diseases and conditions, and to develop case definitions and diagnostic considerations., Methods: Discussions were informed by four reviews on 1) periodontal manifestions of systemic diseases and conditions; 2) mucogingival conditions around natural teeth; 3) traumatic occlusal forces and occlusal trauma; and 4) dental prostheses and tooth related factors. This consensus report is based on the results of these reviews and on expert opinion of the participants., Results: Key findings included the following: 1) there are mainly rare systemic conditions (such as Papillon-Lefevre Syndrome, leucocyte adhesion deficiency, and others) with a major effect on the course of periodontitis and more common conditions (such as diabetes mellitus) with variable effects, as well as conditions affecting the periodontal apparatus independently of dental plaque biofilm-induced inflammation (such as neoplastic diseases); 2) diabetes-associated periodontitis should not be regarded as a distinct diagnosis, but diabetes should be recognized as an important modifying factor and included in a clinical diagnosis of periodontitis as a descriptor; 3) likewise, tobacco smoking - now considered a dependence to nicotine and a chronic relapsing medical disorder with major adverse effects on the periodontal supporting tissues - is an important modifier to be included in a clinical diagnosis of periodontitis as a descriptor; 4) the importance of the gingival phenotype, encompassing gingival thickness and width in the context of mucogingival conditions, is recognized and a novel classification for gingival recessions is introduced; 5) there is no evidence that traumatic occlusal forces lead to periodontal attachment loss, non-carious cervical lesions, or gingival recessions; 6) traumatic occlusal forces lead to adaptive mobility in teeth with normal support, whereas they lead to progressive mobility in teeth with reduced support, usually requiring splinting; 7) the term biologic width is replaced by supracrestal tissue attachment consisting of junctional epithelium and supracrestal connective tissue; 8) infringement of restorative margins within the supracrestal connective tissue attachment is associated with inflammation and/or loss of periodontal supporting tissue. However, it is not evident whether the negative effects on the periodontium are caused by dental plaque biofilm, trauma, toxicity of dental materials or a combination of these factors; 9) tooth anatomical factors are related to dental plaque biofilm-induced gingival inflammation and loss of periodontal supporting tissues., Conclusion: An updated classification of the periodontal manifestations and conditions affecting the course of periodontitis and the periodontal attachment apparatus, as well as of developmental and acquired conditions, is introduced. Case definitions and diagnostic considerations are also presented., (© 2018 American Academy of Periodontology and European Federation of Periodontology.)
- Published
- 2018
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75. Clinical Management of Patients With Diabetes and Periodontal Disease: Ideas Whose Time Has Come.
- Author
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Lalla E
- Subjects
- Diabetes Complications diagnosis, Diabetes Mellitus diagnosis, Humans, Periodontal Diseases therapy, Diabetes Complications therapy, Periodontal Diseases complications
- Abstract
Multiple studies over many decades have demonstrated that diabetes mellitus and periodontitis are closely linked and may amplify one another. This review provides a different look at the complex association between these two common, chronic conditions and discusses decision-making in the management of affected individuals.
- Published
- 2017
76. Increased levels of soluble CD163 in periodontitis patients.
- Author
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Detzen L, Chen SCY, Cheng B, Papapanou PN, and Lalla E
- Subjects
- Adult, Aged, Antigens, CD genetics, Antigens, Differentiation, Myelomonocytic genetics, Biomarkers blood, Cross-Sectional Studies, Female, Gene Expression, Gingiva, Humans, Male, Middle Aged, New York, Periodontal Index, RNA, Messenger biosynthesis, RNA, Messenger blood, Receptors, Cell Surface genetics, Saliva chemistry, Young Adult, Antigens, CD blood, Antigens, Differentiation, Myelomonocytic blood, Periodontitis metabolism, Receptors, Cell Surface blood
- Abstract
Aim: Soluble CD163 (sCD163) has been implicated as a new biomarker in inflammatory conditions. The aim of this cross-sectional study was to assess CD163 levels systemically and locally in patients with chronic periodontitis., Methods: sCD163 levels were measured by ELISA in serum samples from 70 periodontitis and 70 periodontally healthy subjects, and in saliva samples in a subset of the population. Two gingival biopsies were harvested per subject from 20 periodontitis patients: one from a periodontally affected site, the other from a healthy site, and the relative expression of CD163 mRNA was assessed by real-time PCR., Results: Serum sCD163 was significantly higher in periodontitis patients compared to periodontally healthy subjects (720.0 ± 330.6 ng/ml versus 510.7 ± 219.6 ng/ml, respectively; p < .001). Similarly, sCD163 levels in saliva were significantly increased in periodontitis compared to healthy subjects (3.01 ± 5.07 ng/ml versus 1.98 ± 4.95 ng/ml, respectively; p = .009). Serum and saliva sCD163 levels showed a positive correlation (Kendall's tau .27, p = .018). Importantly, CD163 gene expression was significantly higher in affected sites compared to unaffected sites in periodontitis patients, with a mean fold upregulation of 9.9 (STD: 15.3, p = .010)., Conclusion: Our findings suggest that CD163 may be involved in the pathogenesis of periodontitis and its link with systemic conditions., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2017
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77. Six-month outcomes in dental patients identified with hyperglycaemia: a randomized clinical trial.
- Author
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Lalla E, Cheng B, Kunzel C, Burkett S, Ferraro A, and Lamster IB
- Subjects
- Adult, Aged, Blood Glucose analysis, Body Weight, Consumer Health Information, Exercise, Feeding Behavior, Female, Follow-Up Studies, Glycated Hemoglobin analysis, Health Behavior, Humans, Hyperglycemia prevention & control, Life Style, Male, Middle Aged, Patient Acceptance of Health Care, Patient Education as Topic methods, Periodontal Index, Periodontal Pocket diagnosis, Periodontal Pocket prevention & control, Prediabetic State diagnosis, Prediabetic State prevention & control, Referral and Consultation, Risk Assessment, Risk Factors, Tooth Loss diagnosis, Treatment Outcome, Dental Care, Hyperglycemia diagnosis, Mass Screening
- Abstract
Aim: To assess an approach to improving behavioural and glycaemic outcomes in dental patients who present with diabetes risk factors and previously unrecognized hyperglycaemia., Methods: We randomized 101 individuals identified with potential diabetes or pre-diabetes into two interventions. In the basic/control intervention, participants were informed about their diabetes risk factors and blood test result, and advised to see a physician. In the enhanced/test intervention, patients received a detailed explanation of findings and their implications, a written report for the physician, and were contacted at 2 and 4 months to inquire whether medical follow-up had occurred. At a 6-month re-evaluation, outcome measures included visit to physician, positive lifestyle changes and reduction in HbA1c., Results: Seventy-three subjects returned for the 6-month visit. The two intervention groups did not significantly differ in any of the outcome variables. Eighty-four percent of subjects reported having visited a physician post-randomization, and 49% reported at least one positive lifestyle change as a result of our intervention. In subjects identified with potential diabetes (baseline HbA1c ≥ 6.5%), HbA1c was reduced 1.46 ± 0.28% compared to baseline (p < 0.01)., Conclusion: Diabetes risk assessment and education by dental professionals of affected individuals unaware of their status may contribute to improved patient outcomes., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
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78. Periodontal findings in individuals with newly identified pre-diabetes or diabetes mellitus.
- Author
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Lamster IB, Cheng B, Burkett S, and Lalla E
- Subjects
- Adult, Black or African American, Age Factors, Aged, Asian, Blood Glucose analysis, Cohort Studies, Gingival Hemorrhage classification, Glycated Hemoglobin analysis, Humans, Hypercholesterolemia complications, Hypertension complications, Middle Aged, Obesity complications, Overweight complications, Periodontal Pocket classification, Prediabetic State complications, Tooth Loss classification, White People, Diabetes Mellitus diagnosis, Periodontal Index, Prediabetic State diagnosis
- Abstract
Aim: To assess the periodontal status and number of missing teeth in patients with newly identified pre-diabetes or diabetes mellitus., Methods: A total of 1097 subjects with previously undiagnosed diabetes were available for study, and were categorized into normoglycaemic, potentially pre-diabetes or potentially diabetes groups based on a point-of-care (POC) HbA1c test., Results: In fully adjusted models, significant differences were observed between all groups for the per cent of teeth with at least one site with a probing depth of ≥5 mm. For bleeding on probing, there were significant differences between diabetes and pre-diabetes (p = 0.001), and between diabetes and normoglycaemic groups (p = 0.002). For missing teeth, there were significant differences between the pre-diabetes and normoglycaemic groups (p = 0.034), and the diabetes and normoglycaemic groups (p = 0.004)., Conclusions: Individuals with previously unidentified pre-diabetes demonstrate a level of periodontal destruction between that observed for normoglycaemic individuals and persons with diabetes. These data emphasize the association of oral findings to dysglycaemia, and suggest that periodontal disease and tooth loss can be early complications of diabetes mellitus., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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79. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes.
- Author
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Taylor JJ, Preshaw PM, and Lalla E
- Subjects
- Animals, Blood Glucose, Humans, Interleukin-1, Interleukin-6, Periodontium metabolism, Diabetes Mellitus, Periodontitis
- Abstract
Aims: To review the evidence for the molecular and cellular processes that may potentially link periodontal disease and diabetes. The pathogenic roles of cytokines and metabolic molecules (e.g. glucose, lipids) are explored and the role of periodontal bacteria is also addressed. Paradigms for bidirectional relationships between periodontitis and diabetes are discussed and opportunities for elaborating these models are considered., Methods: Database searches were performed using MeSH terms, keywords, and title words. Studies were evaluated and summarized in a narrative review., Results: Periodontal microbiota appears unaltered by diabetes and there is little evidence that it may influence glycaemic control. Small-scale clinical studies and experiments in animal models suggest that IL-1b, TNF-a, IL-6, OPG and RANKL may mediate periodontitis in diabetes. The AGE-RAGE axis is likely an important pathway of tissue destruction and impaired repair in diabetes-associated periodontitis. A role for locally activated pro-inflammatory factors in the periodontium, which subsequently impact on diabetes, remains speculative., Conclusion: There is substantial information on potential mechanistic pathways which support a close association between diabetes and periodontitis, but there is a real need for longitudinal clinical studies using larger patient groups, integrated with studies of animal models and cells/tissues in vitro.
- Published
- 2013
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80. Assessment and management of patients with diabetes mellitus in the dental office.
- Author
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Lalla E and Lamster IB
- Subjects
- Early Diagnosis, Humans, Periodontal Diseases diagnosis, Risk Factors, Dental Care for Chronically Ill methods, Diabetes Complications diagnosis, Periodontal Diseases etiology, Prediabetic State diagnosis
- Abstract
Diabetes mellitus is a serious chronic disease that affects many dental patients. Dental professionals have the potential and responsibility to assume an active role in the early identification, assessment, and management of their patients who present with or are at risk of developing diabetes. Close maintenance, meticulous monitoring of individual patient needs, and close collaboration with other health care professionals involved in the care will enable better control of the oral complications of diabetes and contribute to the better management of the patient's overall health status., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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81. Diabetes and oral disease: implications for health professionals.
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Albert DA, Ward A, Allweiss P, Graves DT, Knowler WC, Kunzel C, Leibel RL, Novak KF, Oates TW, Papapanou PN, Schmidt AM, Taylor GW, Lamster IB, and Lalla E
- Subjects
- Health Personnel, Humans, Mouth Diseases metabolism, Patient Care, Patient Education as Topic, Periodontitis complications, Periodontitis metabolism, Receptor for Advanced Glycation End Products, Receptors, Immunologic metabolism, Diabetes Complications, Diabetes Mellitus genetics, Diabetes Mellitus metabolism, Diabetes Mellitus mortality, Mouth Diseases complications, Periodontal Diseases complications
- Abstract
"Diabetes and Oral Disease: Implications for Health Professionals" was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011 in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the interprofessional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them, and, ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event., (© 2012 New York Academy of Sciences.)
- Published
- 2012
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82. Diabetes mellitus and oral health care: time for the next step.
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Lamster IB, Kunzel C, and Lalla E
- Subjects
- Female, Humans, Male, Blood Glucose analysis, Community-Based Participatory Research, Dental Research methods, Diabetes Mellitus diagnosis, Practice Patterns, Dentists'
- Published
- 2012
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83. Klebsiella pneumoniae induces an inflammatory response in human retinal-pigmented epithelial cells.
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Pollreisz A, Rafferty B, Kozarov E, and Lalla E
- Subjects
- Cell Line, Chemokine CCL2 biosynthesis, Humans, Interleukin-6 biosynthesis, Klebsiella Infections immunology, Lipopolysaccharides immunology, Retinal Pigment Epithelium immunology, Retinitis immunology, Host-Pathogen Interactions immunology, Klebsiella Infections microbiology, Klebsiella pneumoniae, Retinal Pigment Epithelium microbiology, Retinitis microbiology
- Abstract
Purpose: The retinal pigment epithelium (RPE) is a barrier to Klebsiella pneumoniae infection in endogenous endophthalmitis. Nevertheless, the inflammatory response of RPE cells upon interaction with this pathogen has not been studied. Here we tested the hypothesis that K. pneumoniae induces an inflammatory response in human retinal epithelial cells., Methods: In this study we set out to investigate the effects of whole K. pneumoniae and of its lipopolysaccharide on RPE cells in vitro using bacterial invasion and cytotoxicity assays, fluorescent microscopy and ELISA. For that, we utilized K. pneumoniae strain ATCC 43816 and the continuous human retinal-pigmented epithelial cell line ARPE-19., Results: Stimulation of ARPE-19 with live K. pneumoniae for 24h induced a 31.5-fold (p=0.0132) increase in IL-6 and 6.5-fold (p=0.0004) increase in MCP-1 levels compared to the non-infected control cells. Purified K. pneumoniae LPS (1μgml(-1)) also induced cytokine levels, MCP-1 (1.7-fold upregulation; p=0.0006) and IL-6 (1.3-fold upregulation, p=0.065). The tested K. pneumoniae strain ATCC 43816 did not have a significant effect on the viability of ARPE-19 cells (11% decrease, p=0.096) and showed a low ability to invade the cells., Conclusions: Both whole live K. pneumoniae and K. pneumoniae LPS exert a strong pro-inflammatory effect on retinal pigmented epithelial cells, consistent with clinical manifestations of disease. Bacterial pro-inflammatory effects are not likely related to host cell invasion. This is the first investigation of the interactions of a major endogenous endophthalmitis pathogen, K. pneumoniae with human retinal pigmented epithelial cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2012
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84. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases.
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Lalla E and Papapanou PN
- Subjects
- Blood Glucose analysis, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 2 complications, Humans, Hyperglycemia complications, Insulin Resistance, Periodontitis therapy, Periodontium chemistry, Receptor for Advanced Glycation End Products, Receptors, Immunologic analysis, Receptors, Immunologic physiology, Risk Factors, Diabetes Complications, Diabetes Mellitus blood, Diabetes Mellitus therapy, Periodontitis complications
- Abstract
Diabetes mellitus (a group of metabolic disorders characterized by hyperglycemia) and periodontitis (a microbially induced inflammatory disorder that affects the supporting structures of teeth) are both common, chronic conditions. Multiple studies have demonstrated that diabetes mellitus (type 1 and type 2) is an established risk factor for periodontitis. Findings from mechanistic studies indicate that diabetes mellitus leads to a hyperinflammatory response to the periodontal microbiota and also impairs resolution of inflammation and repair, which leads to accelerated periodontal destruction. The cell surface receptor for advanced glycation end products and its ligands are expressed in the periodontium of individuals with diabetes mellitus and seem to mediate these processes. The association between the two diseases is bidirectional, as periodontitis has been reported to adversely affect glycemic control in patients with diabetes mellitus and to contribute to the development of diabetic complications. In addition, meta-analyses conclude that periodontal therapy in individuals with diabetes mellitus can result in a modest improvement of glycemic control. The effect of periodontal infections on diabetes mellitus is potentially explained by the resulting increase in levels of systemic proinflammatory mediators, which exacerbates insulin resistance. As our understanding of the relationship between diabetes mellitus and periodontitis deepens, increased patient awareness of the link between diabetes mellitus and oral health and collaboration among medical and dental professionals for the management of affected individuals become increasingly important.
- Published
- 2011
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85. Receptor for advanced glycation endproducts mediates pro-atherogenic responses to periodontal infection in vascular endothelial cells.
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Pollreisz A, Hudson BI, Chang JS, Qu W, Cheng B, Papapanou PN, Schmidt AM, and Lalla E
- Subjects
- Animals, Aorta cytology, Endothelial Cells metabolism, Epitopes, Humans, Inflammation, Male, Mice, Mice, Inbred C57BL, Oxidative Stress, Receptor for Advanced Glycation End Products, Atherosclerosis metabolism, Endothelial Cells pathology, Periodontitis metabolism, Porphyromonas gingivalis metabolism, Receptors, Immunologic genetics, Receptors, Immunologic metabolism
- Abstract
Objective: A link between periodontal infections and an increased risk for vascular disease has been demonstrated. Porphyromonas gingivalis, a major periodontal pathogen, localizes in human atherosclerotic plaques, accelerates atherosclerosis in animal models and modulates vascular cell function. The receptor for advanced glycation endproducts (RAGE) regulates vascular inflammation and atherogenesis. We hypothesized that RAGE is involved in P. gingivalis's contribution to pro-atherogenic responses in vascular endothelial cells., Methods and Results: Murine aortic endothelial cells (MAEC) were isolated from wild-type C57BL/6 or RAGE-/- mice and were infected with P. gingivalis strain 381. P. gingivalis 381 infection significantly enhanced expression of RAGE in wild-type MAEC. Levels of pro-atherogenic advanced glycation endproducts (AGEs) and monocyte chemoattractant protein 1 (MCP-1) were significantly increased in wild-type MAEC following P. gingivalis 381 infection, but were unaffected in MAEC from RAGE-/- mice or in MAEC infected with DPG3, a fimbriae-deficient mutant of P. gingivalis 381. Consistent with a role for oxidative stress and an AGE-dependent activation of RAGE in this setting, both antioxidant treatment and AGE blockade significantly suppressed RAGE gene expression and RAGE and MCP-1 protein levels in P. gingivalis 381-infected human aortic endothelial cells (HAEC)., Conclusion: The present findings implicate for the first time the AGE-RAGE axis in the amplification of pro-atherogenic responses triggered by P. gingivalis in vascular endothelial cells., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
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86. Oral disease experience of older adults seeking oral health services.
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Ahluwalia KP, Cheng B, Josephs PK, Lalla E, and Lamster IB
- Subjects
- Age Factors, Aged, Aged, 80 and over, Chronic Disease, Cross-Sectional Studies, DMF Index, Dental Restoration, Permanent statistics & numerical data, Female, Health Services Accessibility statistics & numerical data, Health Status, Humans, Male, Medicaid statistics & numerical data, Mouth, Edentulous epidemiology, Needs Assessment statistics & numerical data, New York City epidemiology, Patient Acceptance of Health Care statistics & numerical data, Prevalence, Retrospective Studies, Root Caries epidemiology, Sex Factors, Tooth Loss epidemiology, United States epidemiology, Alveolar Bone Loss epidemiology, Dental Care statistics & numerical data, Dental Caries epidemiology
- Abstract
Objective: The objective of this investigation was to describe the dental disease (dental caries and alveolar bone loss) experience in a sample of community-dwelling older adults who regularly utilize dental services in New York City., Background: Public financing for dental care directed at older adults in the United States is minimal. Improved preventive methods, primarily the use of fluorides, have resulted in declines in tooth loss, and concomitant increase in risk for dental diseases among older adults. While the oral disease burden in institutionalized elderly and those unable to access services is well-documented, the dental care needs of older adults who access dental services are not well documented., Materials and Methods: Radiographic and record review were used to determine prevalence of dental caries, alveolar bone loss, frequency of service utilization, and medical status in this cross-sectional investigation of a sample of older adults (N = 200) using dental services at Columbia University College of Dental Medicine., Results: Only 9% of the sample was completely edentulous, the mean DMFT was 19.9 and mean alveolar bone loss was 3.6 mm. Missing and Decayed Teeth accounted for 57.8% and 6.5% of the total caries burden respectively. Missing Teeth and alveolar bone loss increased with increasing age, but there was no increase in Decayed Teeth., Conclusions: While access to and utilization of dental services may result in improved tooth retention, older adults who use dental services continue to have dental care needs, especially periodontal care needs.
- Published
- 2010
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87. Knowledge and orientations of internal medicine trainees toward periodontal disease.
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Quijano A, Shah AJ, Schwarcz AI, Lalla E, and Ostfeld RJ
- Subjects
- Adult, Attitude of Health Personnel, Chi-Square Distribution, Female, Humans, Internship and Residency, Male, Statistics, Nonparametric, Surveys and Questionnaires, Health Knowledge, Attitudes, Practice, Internal Medicine education, Periodontal Diseases psychology, Students, Medical psychology
- Abstract
Background: There is growing evidence that periodontal disease may be a source of systemic inflammation that impacts overall health. As such, periodontal disease is associated with an increased risk of systemic illnesses such as cardiovascular disease and adverse outcomes in diabetes mellitus and pregnancy. With the aim of assessing oral health knowledge and orientations of physicians in training, we surveyed incoming internal medicine trainees about their general knowledge, attitudes, and behaviors/practices about periodontal health and disease., Methods: A 16-question survey was distributed during orientation to incoming internal medicine trainees at a single urban teaching hospital in New York City in 2007 and 2008. Questions aimed to assess the knowledge levels of the subjects about periodontal disease and their attitudes toward discussing/evaluating the periodontal status of their patients. The study was approved by the Montefiore Institutional Review Board., Results: Of 125 incoming medical trainees queried, 115 responded (92% response rate). Of the 115 responders, 96% were medical interns. The median age of the trainees was 27 years (interquartile range: 26 to 29 years), and 61% were female. Overall, 34% of the trainees answered all five true/false general knowledge questions correctly, 82% reported that they never asked patients if they were diagnosed with periodontal disease, 90% reported not receiving any training about periodontal disease during medical school, 69% reported that they were not comfortable at all performing a simple periodontal examination, 17% agreed that patients expect physicians to discuss/screen for periodontal disease, 46% felt that discussing/evaluating the periodontal status of their patients was peripheral to their role as physicians, 76% reported never screening patients for periodontal disease, and 23% stated that they never referred patients to dentists., Conclusions: In this study, incoming internal medicine trainees had inadequate knowledge regarding periodontal disease. They were also generally uncomfortable with performing a simple periodontal examination. Oral health training in medical school and the medical postgraduate setting is recommended.
- Published
- 2010
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88. Inflammatory stress in primary venous and aortic endothelial cells of type 1 diabetic mice.
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Bucciarelli LG, Pollreisz A, Kebschull M, Ganda A, Kalea AZ, Hudson BI, Zou YS, Lalla E, Ramasamy R, Colombo PC, Schmidt AM, and Yan SF
- Subjects
- Animals, Aorta pathology, Apoptosis, Caspase 1 genetics, Cell Separation, Cells, Cultured, Diabetes Mellitus, Experimental genetics, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 pathology, Endothelial Cells pathology, Gene Expression Profiling, Gene Expression Regulation, Inflammation genetics, Inflammation pathology, Interleukin-1beta genetics, Male, Mice, Mice, Inbred C57BL, Phenotype, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Stress, Physiological genetics, Time Factors, Vena Cava, Inferior pathology, Aorta immunology, Diabetes Mellitus, Experimental immunology, Diabetes Mellitus, Type 1 immunology, Endothelial Cells immunology, Inflammation immunology, Inflammation Mediators metabolism, Stress, Physiological immunology, Vena Cava, Inferior immunology
- Abstract
Objective: The progression of diabetes is associated with profound endothelial dysfunction. We tested the hypothesis that cellular stress would be detectable in ECs retrieved from arterial and venous vessels of diabetic mice., Method: We describe a method for direct isolation of well-characterised aortic and venous ECs from mice in which cells are not subjected to propagation in culture., Results: Gene expression profiling, confirmed by real-time PCR, revealed a progressive increase in markers of injury within two main gene families, EC activation and EC apoptosis, in aortic and venous ECs recovered from diabetic versus non-diabetic mice. In short-term diabetes, Il1b mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls. In long-term diabetes, casp-1 mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls., Conclusion: These data suggest that diabetes imparts diffuse endothelial perturbation in the arterial and venous endothelium.
- Published
- 2009
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89. Heterogeneity of systemic inflammatory responses to periodontal therapy.
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Behle JH, Sedaghatfar MH, Demmer RT, Wolf DL, Celenti R, Kebschull M, Belusko PB, Herrera-Abreu M, Lalla E, and Papapanou PN
- Subjects
- Adiponectin blood, Adolescent, Adult, Aged, Alveolar Bone Loss blood, Alveolar Bone Loss surgery, Alveolar Bone Loss therapy, Antibodies, Bacterial blood, C-Reactive Protein analysis, Dental Plaque microbiology, Dental Scaling, E-Selectin blood, Female, Humans, Intercellular Adhesion Molecule-1 blood, Interleukins blood, Linear Models, Male, Matrix Metalloproteinase 9 blood, Middle Aged, Oral Hygiene education, Periodontitis surgery, Peroxidase blood, Plasminogen Activator Inhibitor 1 blood, Prospective Studies, Serum Amyloid P-Component analysis, Tumor Necrosis Factor-alpha blood, Vascular Cell Adhesion Molecule-1 blood, Young Adult, Cardiovascular Diseases blood, Inflammation blood, Inflammation Mediators blood, Periodontitis blood, Periodontitis therapy
- Abstract
Aims: We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers., Material and Methods: Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: 1-week pre-therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed the plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analysed using checkerboard hybridizations., Results: At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite summary inflammatory score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced a marked reduction and a pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis., Conclusions: Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.
- Published
- 2009
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90. Porphyromonas gingivalis infection and prothrombotic effects in human aortic smooth muscle cells.
- Author
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Roth GA, Aumayr K, Giacona MB, Papapanou PN, Schmidt AM, and Lalla E
- Subjects
- Bacterial Adhesion, Humans, Lipoproteins analysis, Lipoproteins biosynthesis, Muscle, Smooth, Vascular cytology, Thromboplastin analysis, Aorta microbiology, Muscle, Smooth, Vascular microbiology, Myocytes, Smooth Muscle microbiology, Porphyromonas gingivalis pathogenicity, Thrombosis etiology
- Abstract
Introduction: Accumulating evidence has demonstrated an association between periodontal infectious agents, such as Porphyromonas gingivalis, and vascular disease. Tissue factor (TF) and its specific tissue factor pathway inhibitor (TFPI) are produced by vascular cells and are important regulators of the coagulation cascade., Materials and Methods: To assess the role of P. gingivalis in atherothrombosis, we infected primary human aortic smooth muscle cells (HASMC) with either P. gingivalis 381, its non-invasive mutant DPG3, or heat-killed P. gingivalis 381. Levels and activity of TF and TFPI were measured 8 and 24 hours after infection in cell extracts and cell culture supernatants., Results: P. gingivalis 381 did not affect total TF antigen or TF activity in HASMC, but it significantly suppressed TFPI levels and activity compared to uninfected control cells, and those infected with the non-invasive mutant strain or the heat-killed bacteria. Further, P. gingivalis' LPS (up to a concentration of 5 microg/ml) failed to induce prothrombotic effects in HASMC, suggesting a significant role for the ability of whole viable bacteria to invade this cell type., Conclusion: These data demonstrate for the first time that infection with a periodontal pathogen induces a prothrombotic response in HASMC.
- Published
- 2009
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91. The relationship between oral health and diabetes mellitus.
- Author
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Lamster IB, Lalla E, Borgnakke WS, and Taylor GW
- Subjects
- Blood Glucose metabolism, Diabetes Complications metabolism, Diabetes Mellitus metabolism, Humans, Mouth Diseases diagnosis, Mouth Diseases metabolism, Diabetes Complications diagnosis, Diabetes Mellitus classification, Mouth Diseases complications, Oral Health
- Abstract
Background: The term "diabetes mellitus" describes a group of disorders characterized by elevated levels of glucose in the blood and abnormalities of carbohydrate, fat and protein metabolism. A number of oral diseases and disorders have been associated with diabetes mellitus, and periodontitis has been identified as a possible risk factor for poor metabolic control in subjects with diabetes., Methods: The authors reviewed the literature to identify oral conditions that are affected by diabetes mellitus. They also examined the literature concerning periodontitis as a modifier of glycemic control., Results: Although a number of oral disorders have been associated with diabetes mellitus, the data support the fact that periodontitis is a complication of diabetes. Patients with long-standing, poorly controlled diabetes are at risk of developing oral candidiasis, and the evidence indicates that periodontitis is a risk factor for poor glycemic control and the development of other clinical complications of diabetes. Evidence suggests that periodontal changes are the first clinical manifestation of diabetes., Conclusions: Diabetes is an important health care problem. The evidence suggests that oral health care providers can have a significant, positive effect on the oral and general health of patients with diabetes mellitus.
- Published
- 2008
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92. Management of patients with diabetes by general dentists in New Zealand.
- Author
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Forbes K, Thomson WM, Kunzel C, Lalla E, and Lamster IB
- Subjects
- Adult, Attitude of Health Personnel, Cohort Studies, Communication, Cross-Sectional Studies, Dentist-Patient Relations, Diabetes Complications, Education, Dental, Education, Dental, Continuing, Female, General Practice, Dental, Humans, Male, Mass Screening, Medical History Taking, Middle Aged, Mouth Diseases complications, New England, New Zealand, Referral and Consultation, Sex Factors, Dental Care for Chronically Ill, Dentists psychology, Diabetes Mellitus diagnosis, Diabetes Mellitus therapy
- Abstract
Background: The prevalence of diabetes in New Zealand is reaching epidemic proportions, with serious implications for oral health. We investigated the attitudes, beliefs, and practices of New Zealand (NZ) general dental practitioners (GDPs) with respect to the management of patients with diabetes and contrasted the NZ findings with those from a similar survey of GDPs in the Northeast United States (NE US) conducted in 2002., Methods: A nationwide postal survey was conducted of NZ dentists. A random sample was selected from the 2005 New Zealand Dental Register. Responses were received from 437 dentists (response rate: 64.5%)., Results: The sample was representative. Most GDPs participated in the assessment and discussion phases of managing patients with diabetes, but the prevalence of more hands-on activities (such as testing) was considerably lower. Three-quarters of dentists asked new patients about their type of diabetes. Just over two in five respondents believed that their evaluation and/or management of the patient with diabetes were hindered by the lack of continuing education opportunities. Almost one-third of dentists were unwilling to screen for diabetes using a finger-stick test, and only 2.6% overall had ever done so. There were only minor differences between NZ and NE US dentists., Conclusion: Given the increasing numbers of patients with diabetes (known and unknown), there is a need for NZ and US dentists to be more involved in their active management.
- Published
- 2008
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93. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice.
- Author
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Harja E, Bu DX, Hudson BI, Chang JS, Shen X, Hallam K, Kalea AZ, Lu Y, Rosario RH, Oruganti S, Nikolla Z, Belov D, Lalla E, Ramasamy R, Yan SF, and Schmidt AM
- Subjects
- Animals, Atherosclerosis genetics, Atherosclerosis pathology, Disease Models, Animal, Endothelium, Vascular injuries, Endothelium, Vascular pathology, Epitopes genetics, Epitopes metabolism, Glycation End Products, Advanced genetics, HMGB1 Protein genetics, HMGB1 Protein metabolism, Humans, Inflammation genetics, Inflammation metabolism, Inflammation pathology, Leukocyte L1 Antigen Complex genetics, Leukocyte L1 Antigen Complex metabolism, Ligands, Mice, Mice, Knockout, Receptor for Advanced Glycation End Products, Receptors, Immunologic genetics, Apolipoproteins E genetics, Atherosclerosis metabolism, Endothelium, Vascular metabolism, Glycation End Products, Advanced metabolism, Receptors, Immunologic immunology
- Abstract
Endothelial dysfunction is a key triggering event in atherosclerosis. Following the entry of lipoproteins into the vessel wall, their rapid modification results in the generation of advanced glycation endproduct epitopes and subsequent infiltration of inflammatory cells. These inflammatory cells release receptor for advanced glycation endproduct (RAGE) ligands, specifically S100/calgranulins and high-mobility group box 1, which sustain vascular injury. Here, we demonstrate critical roles for RAGE and its ligands in vascular inflammation, endothelial dysfunction, and atherosclerotic plaque development in a mouse model of atherosclerosis, apoE-/- mice. Experiments in primary aortic endothelial cells isolated from mice and in cultured human aortic endothelial cells revealed the central role of JNK signaling in transducing the impact of RAGE ligands on inflammation. These data highlight unifying mechanisms whereby endothelial RAGE and its ligands mediate vascular and inflammatory stresses that culminate in atherosclerosis in the vulnerable vessel wall.
- Published
- 2008
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94. Periodontal infections and diabetes mellitus: when will the puzzle be complete?
- Author
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Lalla E
- Subjects
- Blood Glucose physiology, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 drug therapy, Glycated Hemoglobin, Humans, Nitric Oxide blood, Periodontal Diseases blood, Periodontal Diseases therapy, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 2 complications, Periodontal Diseases complications
- Published
- 2007
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95. Gingival bleeding in 6- to 13-year-old children with diabetes mellitus.
- Author
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Lal S, Cheng B, Kaplan S, Softness B, Greenberg E, Goland RS, Lalla E, and Lamster IB
- Subjects
- Adolescent, Body Mass Index, Case-Control Studies, Child, Dental Plaque Index, Dentition, Mixed, Female, Glycated Hemoglobin analysis, Humans, Male, Oral Hygiene, Periodontal Index, Regression Analysis, Diabetes Mellitus, Type 1 complications, Gingival Hemorrhage etiology
- Abstract
Purpose: This study assessed gingival bleeding in diabetic children during the mixed dentition period., Methods: Three hundred fifty-five 6- to 13-year-old diabetic (99% type 1) and nondiabetic control children in the mixed dentition stage were evaluated from a total cohort of 700 6- to 18-year-old children. Gingival status was assessed, and data on important diabetes-related variables were collected. Analyses were performed using Poisson's regression., Results: Diabetic children had significantly more gingival bleeding than controls for both primary and permanent teeth. The risk of gingival bleeding around the primary teeth in cases was 35% more than in the control group (P=.001); and the risk of gingival bleeding around the permanent teeth in cases was 57% more than in the controls (P<.001). The number of teeth with bleeding had a very modest, but statistically significant, association with: (1) mean HbA1c; (2) body mass index (BMI)-for-age percentile; and (3) duration of diabetes., Conclusions: These findings demonstrate that diabetic children are at a significantly higher risk for gingival bleeding. Diabetes-related oral complications affect the primary periodontium as early as age 6 and possibly earlier. The emphasis on oral hygiene may be valuable in preventing future periodontal complications in diabetic patients.
- Published
- 2007
96. Porphyromonas gingivalis infection and cell death in human aortic endothelial cells.
- Author
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Roth GA, Ankersmit HJ, Brown VB, Papapanou PN, Schmidt AM, and Lalla E
- Subjects
- Adenosine Diphosphate analysis, Adenosine Triphosphate analysis, Aorta cytology, Cells, Cultured, Chemokine CCL2 biosynthesis, DNA Fragmentation, Endothelial Cells cytology, Endothelial Cells metabolism, Endothelial Cells pathology, Histones metabolism, Humans, L-Lactate Dehydrogenase analysis, Microscopy, Phase-Contrast, Apoptosis, Endothelial Cells microbiology, Porphyromonas gingivalis growth & development
- Abstract
Porphyromonas gingivalis is a periodontal pathogen that promotes a proatherogenic response in endothelial cells. Cell death responses of human aortic endothelial cells to P. gingivalis at various multiplicities of infection (MOI) were investigated by assessment of cell detachment, histone-associated DNA fragmentation, lactate dehydrogenase release and ADP:ATP ratio. Porphyromonas gingivalis at MOI 1:10-1:100 did not have a cytotoxic effect, but induced apoptotic cell death at MOI 1:500 and 1:1000. Monocyte chemoattractant protein-1 production was significantly enhanced by P. gingivalis at MOI 1:100. At higher MOI, at least in vitro, P. gingivalis mediates endothelial apoptosis, thereby potentially amplifying proatherogenic mechanisms in the perturbed vasculature.
- Published
- 2007
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97. Dentists' management of the diabetic patient: contrasting generalists and specialists.
- Author
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Kunzel C, Lalla E, and Lamster I
- Subjects
- Adult, Diabetes Complications, Female, Health Care Surveys, Health Status, Humans, Male, Middle Aged, Patient Care Planning, United States, Dentists, Diabetes Mellitus, Oral Health, Periodontics, Practice Patterns, Dentists' statistics & numerical data
- Abstract
Objectives: We measured and contrasted general dentists' and periodontists' involvement in 3 areas of managing diabetic patients-assessment of health status, discussion of pertinent issues, and active management of patients--and identified and contrasted predictors of active management of diabetic patients., Methods: We conducted a cross-sectional mail survey of random samples of general dentists and periodontists in the northeastern United States during fall 2002, using lists from the 2001 American Dental Directory and the 2002 American Academy of Periodontology Directory. Responses were received from 105 of 132 eligible general dentists (response rate=80%) and from 103 of 142 eligible periodontists (response rate=73%)., Results: Confidence, involvement with colleagues and medical experts, and professional responsibility were influential predictors of active management for periodontists (R2=0.46, P<.001). Variables pertaining to patient relations were significant predictors for general dentists (R2=0.55, P<.001)., Conclusions: Our findings permitted us to assess and compare general dentists' and periodontists' behavior in 3 realms--assessment of diabetic patients' health status, discussion of pertinent issues, and active management of diabetic patients--and to identify components of potentially effective targeted interventions aimed at increasing specialists' and generalist dentists' involvement in the active management of diabetic patients.
- Published
- 2007
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98. Infection with a periodontal pathogen increases mononuclear cell adhesion to human aortic endothelial cells.
- Author
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Roth GA, Moser B, Roth-Walter F, Giacona MB, Harja E, Papapanou PN, Schmidt AM, and Lalla E
- Subjects
- Aorta microbiology, Bacterial Adhesion, Bacteroidaceae Infections, Cell Adhesion, Cells, Cultured, Cytokines analysis, Humans, Inflammation microbiology, Aorta physiology, Endothelium, Vascular microbiology, Endothelium, Vascular physiology, Periodontitis microbiology, Porphyromonas gingivalis genetics, Porphyromonas gingivalis pathogenicity
- Abstract
Background: As a link between periodontal infections and an increased risk for vascular disease has been demonstrated, we assessed the ability of the Gram-negative periodontal pathogen Porphyromonas gingivalis to modulate properties of endothelial cells linked to inflammation and proatherogenic pathways., Methods and Results: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis strain 381 or its non-invasive fimbriae-deficient mutant, DPG3, and incubated with U-937 monocytes, or Jurkat T cells. P. gingivalis-infected HAEC demonstrated significantly increased adhesion of immune cells compared to non-infected cells or those infected with DPG3. Heat-killed bacteria had no effect on mononuclear cell adhesion and P. gingivalis LPS had only a minimal effect. P. gingivalis infection significantly increased HAEC expression of VCAM-1, ICAM-1 and E-selectin, and enhanced production of IL-6, IL-8 and MCP-1., Conclusion: These data demonstrate that live invasive P. gingivalis 381 elicits a pro-atherogenic response in HAEC.
- Published
- 2007
- Full Text
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99. Management of the patient who smokes and the diabetic patient in the dental office.
- Author
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Kunzel C, Lalla E, and Lamster IB
- Subjects
- Adult, Case Management, Diabetes Complications, Diabetes Mellitus psychology, Female, General Practice, Dental, Humans, Male, Mid-Atlantic Region, Middle Aged, New England, Periodontics, Risk Assessment, Smoking psychology, Smoking Cessation, Surveys and Questionnaires, Attitude of Health Personnel, Diabetes Mellitus therapy, Periodontitis complications, Practice Patterns, Dentists', Smoking therapy
- Abstract
Background: Approaches to patient care consistent with a greater emphasis on the importance of risk factors associated with periodontal disease should include measures to reduce risk. In this article, we investigate the extent to which periodontists' and general practice dentists' (GPs) behaviors and attitudes reflect current understanding of the most important environmental risk factor for periodontitis (smoking) and the most important systemic disease risk factor for periodontitis (diabetes mellitus)., Methods: A mail survey of active periodontists and GPs in the Northeastern United States was conducted during the fall of 2002. Random samples of periodontists and GPs listed in the designated Northeastern states were drawn from the 2002 American Academy of Periodontology Directory and the 2001 American Dental Directory, respectively. Responses were received from 103 periodontists (for a response rate of 73%) and from 105 GPs (for a response rate of 80%)., Results: Although periodontists generally perform risk identification and management behaviors for patients who smoke or who have diabetes more frequently than GPs, both groups tend to engage in activities that inquire, discuss, and inform more than they tend to undertake measures to control or manage these risk factors. Rates of proactive patient management activities are quite low in both clinician groups., Conclusions: There is a need to increase periodontists' and GPs' involvement in the active management of the patient who smokes and in the diabetic patient. Such actions can be expected to result in improved periodontal and general health outcomes.
- Published
- 2006
- Full Text
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100. On the primary care frontlines: the role of the general practitioner in smoking-cessation activities and diabetes management.
- Author
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Kunzel C, Lalla E, Albert DA, Yin H, and Lamster IB
- Subjects
- Attitude of Health Personnel, Clinical Competence, Health Knowledge, Attitudes, Practice, Humans, New England, Practice Patterns, Dentists', Professional Role, Sampling Studies, Surveys and Questionnaires, Diabetes Mellitus therapy, General Practice, Dental, Smoking Cessation
- Abstract
Background: Advances in understanding the relationship between oral disease and systemic conditions need to be translated into clinical practice. Relevant here is assessing dentists' active involvement in in-office smoking-cessation activities and management of the patient with type 1 or type 2 diabetes., Methods: The authors mailed a survey to a net sample of 132 active general practitioners (GPs) in the northeastern United States during fall 2002. They drew a random sample of GPs listed in the designated states from the 2001 American Dental Association directory. They received 105 responses, for a response rate of 80 percent., Results: With regard to smoking-cessation activities and management of diabetic patients, a majority of GPs reported having a lack of knowledge, viewed such activities as peripheral to their role and disagreed that colleagues and/or patients expected them to perform such activities. More GPs performed both activities on an assessing/advising basis than on an active management basis., Conclusion: Results suggest that approaches to changing dentists' behavior should aim not only at increasing knowledge but at overcoming attitudes and orientations associated with actively managing patients who smoke and patients who have diabetes., Practice Implications: The profession's growing evidence base supports an increased primary and preventive care role for dentists. This role affords them opportunities to expand the bounds of dental practice, improve therapeutic outcomes and promote patients' overall health.
- Published
- 2005
- Full Text
- View/download PDF
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