Publications by authors named "Paulo Mascarenhas"

23 Publications

  • Page 1 of 1

Comparing Assessment Tools as Candidates for Personalized Nutritional Evaluation of Senior Citizens in a Nursing Home.

Nutrients 2021 Nov 20;13(11). Epub 2021 Nov 20.

Grupo de Patologia Médica, Nutrição e Exercício Clínico (PaMNEC) do Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), 2829-511 Almada, Portugal.

Nutrition is an important health issue for seniors. In nursing homes, simple, inexpensive, fast, and validated tools to assess nutritional risk/status are indispensable. A multisurvey cross-sectional study with a convenient sample was created, comparing five nutritional screening/assessment tools and the time required for each, in order to identify the most useful instrument for a nursing home setting. Nutrition risk/status was evaluated using the following tools: Subjective Global Assessment (SGA), Mini Nutritional Assessment Short Form (MNA-SF), Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening 2002 (NRS 2002), and calf girth (CG). The time spent completing each tool was recorded. Eighty-three subjects were included. MNA-SF and CG were the screening tools that ranked highest with regards to malnutrition identification. CG failed to identify nutritional risk/malnutrition in seniors with lower limb edema. CG was the fastest tool while SGA was the slowest. This was the first study comparing non-invasive nutritional tools with time expended as a consideration in the implementation. CG is responsive, fast, and reliable in elders without edema. MNA-SF was more efficient at detecting malnutrition cases in the elderly population. Both MNA-SF and CG are considered the most suitable for the nursing home setting.
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http://dx.doi.org/10.3390/nu13114160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623379PMC
November 2021

The prevalence of molar-incisor hypomineralization: a systematic review and meta-analysis.

Sci Rep 2021 11 17;11(1):22405. Epub 2021 Nov 17.

Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz - Cooperativa de Ensino Superior, CRL, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511, Almada, Portugal.

Molar-Incisor Hypomineralization (MIH) is a qualitative defect of enamel of unknown etiology, affecting one or more permanent molars and may include incisors. This condition is a clinical challenge and its prevalence is still uncertain given the recent increase in research. Thus, we aimed to comprehensively estimate the overall prevalence of MIH and associated characteristics. This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We searched articles using PubMed, MEDLINE, CENTRAL, Web of Science, SciELO, LILACS and TRIP databases, until July 2021. Heterogeneity and publication bias were computed via I test statistics and Egger's significance test, respectively. Random-effects meta-analysis of prevalence were processed. We used the Strength of Recommendation Taxonomy [SORT] to grading the strength of evidence. Overall, 116 observational studies were included, with one study with moderate methodological quality and the remaining of high methodological quality. Subgroup analysis confirmed an influence of not using the 2003 MIH case definition (p = 0.0066). The pooled prevalence of MIH was 13.5% (95% CI 12.0-15.1, I = 98.0%). Affected incisors were seen in 36.6% (95% CI 30.0-43.7, I = 92.5%) of the cases. Lastly, the prevalence of hypomineralization of the second primary molars was observed in 3.6% of the MIH cases (95% CI 1.9-6.8, I = 96.3%). America was the continent with highest prevalence (15.3, 95% CI 12.8-18.3, p < 0.001, I = 96.3%) and Asia had the lowest prevalence (10.7, 95% CI 8.5-13.5, p < 0.001, I = 98.7%), however no continental differences were found. Sample size and year of publication were slight contributing factors to the heterogeneity in the analysis. Overall, these results were classified with a SORT A recommendation.
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http://dx.doi.org/10.1038/s41598-021-01541-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599453PMC
November 2021

Serum C-Reactive Protein and Periodontitis: A Systematic Review and Meta-Analysis.

Front Immunol 2021 28;12:706432. Epub 2021 Jul 28.

Periodontology Unit, University College London (UCL) Eastman Dental Institute, London, United Kingdom.

Periodontitis has been associated with low-grade inflammation as assessed by C-reactive protein (CRP) levels and its treatment can decrease CRP serum levels. The aim of this systematic review was to critically appraise the evidence comparing CRP serum levels (standard and high-sensitivity [hs]) of otherwise healthy patients suffering from periodontitis when compared to controls. The impact of intensive and non-intensive nonsurgical periodontal treatment (NSPT) on hs-CRP was also investigated. Four electronic databases (Pubmed, The Cochrane Central Register of Controlled Trials [CENTRAL], EMBASE and Web of Science) were searched up to February 2021 and the review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No. CRD42020167454). Observational and intervention studies that: 1) evaluated CRP and hs-CRP serum levels in patients with and without periodontitis, and; 2) hs- CRP levels after NSPT were included. Following risk of bias appraisal, both qualitative and quantitative analyses were performed. Pooled estimates were rendered through ratio of means (RoM) random-effects meta-analyses. After screening 485 studies, 77 case-control studies and 67 intervention trials were included. Chronic and aggressive periodontitis diagnoses were consistently associated with higher levels of CRP and hs-CRP (p<0.001). Patients with aggressive periodontitis exhibited on average more than 50% higher levels of CRP (RoM [95% confidence interval [CI]]: 1.56 [1.15; 2.12], p=0.0039) than patients with chronic periodontitis. Intensive NSPT induced an immediate increase of hs-CRP followed by a progressive decrease whilst non-intensive NSPT consistently decreased hs-CRP after treatment up to 180 days (p<0.001). These findings provide robust evidence that periodontitis is associated with systemic inflammation as measured by serum CRP levels. Periodontitis treatment induces a short-term acute inflammatory increase when performed in an intensive session, whilst a progressive reduction up to 6 months was demonstrated when performed in multiple visits.
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http://dx.doi.org/10.3389/fimmu.2021.706432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355591PMC
December 2021

Causal Association between Periodontitis and Parkinson's Disease: A Bidirectional Mendelian Randomization Study.

Genes (Basel) 2021 05 19;12(5). Epub 2021 May 19.

Evidence-Based Hub, CRU, CiiEM, Egas Moniz-Cooperativa de Ensino Superior, CRL, 2829-511 Almada, Portugal.

The latest evidence revealed a possible association between periodontitis and Parkinson's disease (PD). We explored the causal relationship of this bidirectional association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on periodontitis and PD. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and eight non-overlapping SNPs of periodontitis from an additional GWAS for validation purposes. Instrumental variables to explore for the reverse causation included forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B = -0.0003, Standard Error [SE] 0.0003, = 0.26). The eight independent SNPs (B = -0.0000, SE 0.0001, = 0.99) validated this outcome. We also found no association of genetically primed PD towards periodontitis (B = -0.0001, SE 0.0001, = 0.19). These MR study findings do not support a bidirectional causal genetic liability between periodontitis and PD. Further GWAS studies are needed to confirm the consistency of these results.
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http://dx.doi.org/10.3390/genes12050772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159074PMC
May 2021

Network Protein Interaction in the Link between Stroke and Periodontitis Interplay: A Pilot Bioinformatic Analysis.

Genes (Basel) 2021 05 20;12(5). Epub 2021 May 20.

Evidence-Based Hub, Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz-Cooperativa de Ensino Superior, CRL, 2829-511 Caparica, Portugal.

The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein-protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and, ultimately, atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.
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http://dx.doi.org/10.3390/genes12050787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160956PMC
May 2021

Predictors of tooth loss during long-term periodontal maintenance: An updated systematic review.

J Clin Periodontol 2021 08 29;48(8):1019-1036. Epub 2021 May 29.

Evidence-Based Hub, CiiEM, Egas Moniz-Cooperativa de Ensino Superior, Caparica, Almada, Portugal.

Aim: To evaluate the risk factors / predictors of tooth loss in patients with periodontitis who underwent periodontal therapy and long-term periodontal maintenance (PM).

Material And Methods: PubMed, CENTRAL, EMBASE, Web of Science, LILACS and Scholar were searched up to and including September 2020. Studies limited to periodontitis patients who underwent active periodontal therapy (APT) and followed a regular PM programme with 5 years follow-up minimum were eligible for inclusion in this review. Studies were included if they reported data on tooth loss during PM. Random effects meta-analyses of number of tooth loss per patient per year were conducted.

Results: Thirty-six papers regarding thirty-three studies were included in this review, with three prospective 30 retrospective trials. Subgroup meta-analysis showed no differences between prospective and retrospective studies, with an average of 0.1 tooth loss per year per patient (p < 0.001). Maxillary and molar teeth were more susceptible to be extracted during long-term PM. Baseline characteristics (smoking, diabetes mellitus, cardiovascular disease, being male and teeth with furcation lesions) showed no significance as predictor of tooth loss through meta-regression. The percentage of tooth loss due to periodontal reasons ranged from 0.45% to 14.4%. The individual outcomes in each study evidenced different patient-related factors (age and smoking) and tooth-related factors (i.e. tooth type and location) were associated with tooth loss during PM.

Conclusion: The majority of patients undergoing long-term PM have not lost teeth. On average, long-term PM effectively causes the loss of 1 tooth per patient every 10 years. Additional prospective trials may confirm these results.
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http://dx.doi.org/10.1111/jcpe.13488DOI Listing
August 2021

Autogenous Mineralized Dentin versus Xenograft granules in Ridge Preservation for Delayed Implantation in Post-extraction Sites: A Randomized controlled clinical trial with an 18 months follow-up.

Clin Oral Implants Res 2021 Aug 17;32(8):905-915. Epub 2021 Jun 17.

Periodontology Department, Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz (IUEM), Caparica, Portugal.

Objectives: To test primary stability of delayed implants placed in post-extraction ridges preserved with autogenous mineralized dentin matrix (MDM) versus xenograft granules. Clinical, histological and pain experience outcomes were further assessed.

Material And Methods: From March 2018 to July 2020, patients requiring ridge preservation in preparation for delayed implant placement in post-extraction sites were included. Participants were randomly allocated to either the test (MDM) or control group (xenograft granules) prior to ridge preservation. Visual analogue scale and analgesic consumption were measured every day for a week. Six months after preservation, trephine cores were harvested for histomorphometry prior to implant placement. Implants were then placed, and implant stability was measured immediately as well as two months after placement. Marginal bone loss and presence of mucositis/peri-implantitis were registered up to 18 months after prosthetic loading.

Results: Fifty-two patients (66 implants) completed the study. MDM and xenograft groups presented similar primary (77.1 ± 6.9 versus. 77.0 versus. 5.9) and secondary (81.8 ± 5.1 versus. 80.1 ± 3.8) implant stabilities. The percentage of newly formed bone in MDM (47.3%) was significantly higher than xenograft (34.9%) (p < .001), and the proportion of residual graft was significantly lower (12.2% in MDM and 22.1% in xenograft) (p < .001). No significant differences were found as far as clinical, radiographic and patient-related outcomes.

Conclusions: Implants placed in sites preserved with MDM had similar primary stability in comparison to xenograft granules. MDM showed a significantly higher quantity of newly formed bone and lower amount of residual graft in histomorphometry results and equal clinical and patient-related outcomes.
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http://dx.doi.org/10.1111/clr.13765DOI Listing
August 2021

Diagnosis of SARS-Cov-2 Infection by RT-PCR Using Specimens Other Than Naso- and Oropharyngeal Swabs: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2021 Feb 21;11(2). Epub 2021 Feb 21.

Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz-Cooperativa de Ensino Superior CRL, Campus Universitário, Quinta da Granja, 2829-511 Caparica, Portugal.

The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling techniques, yet, these have some limitations such as the complexity of collection. Hence, several other types of specimens that are easier to obtain are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab (CS) against standard specimens (NPS, OPS, or a combination of both). In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December, 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). We identified 1560 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). The remaining index specimens could not be adequately assessed given the lack of studies available. Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity; therefore, these appear to be the best candidates for alternative specimens to NPS/OPS in SARS-CoV-2 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial, since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or at outbreak control spots (e.g., schools, airports, and nursing homes).
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http://dx.doi.org/10.3390/diagnostics11020363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926389PMC
February 2021

Biocompatibility of self-adhesive resin cement with fibroblast cells.

J Prosthet Dent 2021 Apr 15;125(4):705.e1-705.e7. Epub 2021 Feb 15.

Professor, Centro de Investigação interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, Portugal. Electronic address:

Statement Of Problem: Dental cements that release monomers that negatively impact adjacent oral soft tissues may adversely affect clinical outcomes. However, in vitro studies evaluating the cytotoxic and genotoxic potential of substances released from dental cements are lacking.

Purpose: The purpose of this in vitro study was to define and compare the cytotoxicity and genotoxicity of the eluates of a self-adhesive resin cement (RelyX Unicem 2 Automix) autopolymerized and light polymerized with 2 other types of luting cements: a glass ionomer cement (Ketac Cem Easymix) and a resin-modified glass ionomer cement (Ketac Cem Plus).

Material And Methods: The eluates were prepared, and 3T3 mouse fibroblast cells were exposed for 24 hours to serial eluate dilutions of the 3 types of cement. Cytotoxicity was determined by using a cell viability assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays. Genotoxic effects were determined by using the cytokinesis-block micronucleus assay.

Results: Cell viability was higher in the presence of the glass ionomer cement eluate than of the resin-modified glass ionomer cement and resin cement eluates. A pronounced decrease in viability was found when the cells were exposed to undiluted samples of resin-modified glass ionomer cement (around 50%) or resin cement (around 80% to 90%). No significant difference in cell viability was found between autopolymerized and light-polymerized resin cements. All cements induced a dose-dependent response of mononucleated cell formation. However, only the resin cements showed double strand breaks significant differences in the deoxyribonucleic acid (DNA) molecules against the basal DNA lesions that occurred spontaneously.

Conclusions: The glass ionomer cement was not found to be cytotoxic or genotoxic, whereas the eluates derived from the resin-modified glass ionomer cement and resin cement, independently of the polymerization method, were cytotoxic in fibroblast cells. Maximum cytotoxicity was observed in the presence of resin cement, which also showed genotoxicity, independently of being light polymerized.
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http://dx.doi.org/10.1016/j.prosdent.2021.01.002DOI Listing
April 2021

Network Protein Interaction in Parkinson's Disease and Periodontitis Interplay: A Preliminary Bioinformatic Analysis.

Genes (Basel) 2020 11 23;11(11). Epub 2020 Nov 23.

Periodontology Department, Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz (IUEM), 2829-511 Caparica, Portugal.

Recent studies supported a clinical association between Parkinson's disease (PD) and periodontitis. Hence, investigating possible interactions between proteins associated to these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins with variants strongly associated with PD and periodontitis. Genes of interest were collected via the Genome-Wide Association Studies (GWAS) database. Then, we conducted a protein interaction analysis, using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, with a highest confidence cutoff of 0.9 and sensitivity analysis with confidence cutoff of 0.7. Our protein network casts a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted, giving the limitations of this approach.
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http://dx.doi.org/10.3390/genes11111385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700320PMC
November 2020

A systematic review and meta-analysis on Bolton's ratios: Normal occlusion and malocclusion.

J Orthod 2020 03 13;47(1):7-29. Epub 2019 Nov 13.

Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Egas Moniz - Cooperativa de Ensino Superior, C.R.L., Monte de Caparica, Almada, Portugal.

Introduction: The purpose of this study was to seek and summarise the Bolton overall index (OI) and anterior index (AI) regarding normal occlusion and Angle's malocclusion according to gender, and to assess if these indices support Bolton's standards as general references.

Methods: PubMed, LILACS, Embase, CENTRAL and Google Scholar databases were searched up to June 2019 (CRD42018088438). Non-randomised clinical studies, published in English and assessing Bolton's OI and/or AI in normal occlusion and Angle's malocclusion groups, were included. OI and AI means, sample size and SDs were collected. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the risk of bias. Pairwise random-effects and multilevel Bayesian network meta-analyses were used to synthesise available data.

Results: Fifty-three observational studies were included (11,411 participants; 3746 men, 4430 women; 15 studies lacked gender information). For normal occlusion, pooled estimates for OI and AI means were 91.78% (95% confidence interval [CI] = 91.42-92.14; I = 92.87%) and 78.25% (95% CI = 77.87-78.62; I = 90.67%), respectively. We could identify in Angle's Class III patients meaningful OI and AI mean deviations from normal occlusion (0.76, 95% credible interval [CrI] = 0.55-0.98 and 0.61, 95% CrI = 0.35-0.87, respectively), while in Class II patients we found a meaningful mean deviation from normal occlusion only for OI (-0.28, 95% CrI = -0.52--0.05). Concerning gender impact, male patients presented higher OI (0.30, 95% CI = 0.00-0.59) and AI (0.41, 95% CI = 0.00-0.83) mean values than female patients in Class I.

Conclusion: Normal occlusion OI and AI mean values differ from Bolton's original values. Class II division 2, for OI mean values, and Class III, for both OI and AI, are proportionally larger than normal occlusion patients. Gender had almost no impact on teeth mesiodistal proportion.
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http://dx.doi.org/10.1177/1465312519886322DOI Listing
March 2020

In vitro and in silico evaluations of resin-based dental restorative material toxicity.

Clin Oral Investig 2020 Aug 12;24(8):2691-2700. Epub 2019 Nov 12.

Centro de investigação interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Quinta da Granja, 2829-511, Caparica, Portugal.

Objectives: This study aims to evaluate the cytocompatibility of three provisional restoration materials and predict neurotoxic potential of their monomers. These materials are Tab 2000® (methyl methacrylate based), ProTemp 4™ (bis-acrylic based) and Structur 3® (urethane dimethacrylate based).

Materials And Methods: Resin samples were incubated in a cell culture medium and the cytotoxic effects of these extracts were studied in 3T3 fibroblast cells through MTT and crystal violet assays as well as ROS assessment. The presence of relevant leached monomers was determined by HPLC. Additionally, the blood-brain barrier (BBB) permeability to these resin-based monomers was predicted using ACD/Labs algorithms model.

Results: Cell survival rates were compared with the resin extracts, and Structur 3® was statistically significant different from the others (p < 0.001) at all-time incubation periods. All materials induced a dose-dependent loss of cell viability; however, only Structur 3 extracts were cytotoxic against 3T3 fibroblasts. The highest cytotoxic effect (77%, p < 0.001) was observed at 24 h incubation period, which may be associated with the presence of urethane dimethacrylate (UDMA) leached monomers. Furthermore, the computational model showed that most monomers under study are expectedly capable of crossing the BBB.

Conclusions: Our results showed that Structur 3® is not cytocompatible with our cell model and UDMA is a potential neurotoxic compound.

Clinical Relevance: These results indicate that only ProTemp 4™ and Tab 2000® are safe for provisional restorations.
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http://dx.doi.org/10.1007/s00784-019-03131-4DOI Listing
August 2020

Fine-tuning multilevel modeling of risk factors associated with nonsurgical periodontal treatment outcome.

Braz Oral Res 2019 Aug 26;33:e081. Epub 2019 Aug 26.

Clinical Research Unit, Almada, Portugal.

This retrospective study evaluated the influence of known risk factors on nonsurgical periodontal treatment (NSPT) response using a pocket depth fine-tuning multilevel linear model (MLM). Overall, 37 patients (24 males and 13 females) with moderate-to-severe chronic periodontitis underwent NSPT. Follow-up visits at 3, 6, and 12 months included measurements of several clinical periodontal parameters. Data were sourced from a previously reported database. In a total of 1416 initially affected sites (baseline PD ≥ 4 mm) on 536 teeth, probing depth (PD) and clinical attachment loss (CAL) reductions after NSPT were evaluated against known risk factors at 3 hierarchical levels (patient, tooth, and site). For each post-treatment follow-up, the variance component models fitted to evaluate the 3-level variance of PD and CAL decrease revealed that all levels contributed significantly to the overall variance (p < 0.001). Patients who underwent NSPT and were continually monitored had curative results. All 3 hierarchical levels included risk factors influencing the degree of PD and CAL reduction. Specifically, the type of tooth, surfaces involved, and tooth mobility site-level risk factors had the strongest impact on these reductions and were highly relevant for the success of NSPT.
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http://dx.doi.org/10.1590/1807-3107bor-2019.vol33.0081DOI Listing
August 2019

Stress, salivary cortisol and periodontitis: A systematic review and meta-analysis of observational studies.

Arch Oral Biol 2018 Dec 30;96:58-65. Epub 2018 Aug 30.

Clinical Research Unit (CRU), Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Campus Universitário, Monte da Caparica, 2829-511 Caparica, Portugal.

Objective: This meta-analysis aims to systematically assess whether periodontitis has a meaningful effect on salivary cortisol, reflecting changes on free blood cortisol levels.

Design: The Cochrane Handbook and the PRISMA statement were used as reporting guidelines. The MEDLINE-PubMed, Google Scholar, EMBASE, and CENTRAL databases were searched until September 2017 to identify eligible studies, screened by seven independent authors and verified by an eighth. Studies comparing salivary cortisol level of periodontitis cases to controls were included. Data were extracted using a predefined table and since all papers were non-randomized clinical trials they were appraised using Downs and Black tool. DerSimonian random effects meta-analysis was performed using OpenMetaAnalyst.

Results: Six cross-sectional studies were included, with 258 participants with chronic periodontitis and 72 with aggressive periodontitis, in a total of 573 participants. Overall results showed that aggressive periodontitis patients have, on average, 53% higher salivary cortisol levels than healthy controls 1.53 (1.11-2.12). Meta-regression exploring the relationship among salivary cortisol levels and periodontal measures, i.e., periodontitis severity, showed a global neutral effect, although this result requires future confirmation due to the low power of the model.

Conclusion: Observational studies results suggest that subjects with aggressive periodontitis have higher salivary cortisol levels than healthy ones or patients with chronic periodontitis. Such salivary cortisol response difference may have a negative impact on the periodontium, contributing to worse the burden of aggressive periodontitis disease. In the future, wide and well-designed longitudinal studies should be carried out in order to extensively confirm this possible effect, considering the complex nature of periodontitis and its many confounders factors that may contribute to this outcome.
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http://dx.doi.org/10.1016/j.archoralbio.2018.08.016DOI Listing
December 2018

Anthropometric features as predictors of atherogenic dyslipidemia and cardiovascular risk in a large population of school-aged children.

PLoS One 2018 1;13(6):e0197922. Epub 2018 Jun 1.

Centro de Genética Médica e Nutrição Pediátrica Egas Moniz, Campus Universitário, Monte da Caparica, Portugal.

Background: Autopsy studies reveal that atherosclerosis lesions can be found as early as two years of age. To slow the development of this early pathology, obesity and dyslipidemia prevention should start from childhood making it urgent to explore new ways to evaluate dyslipidemia risk in children that can be applied widely, such as the non-invasive anthropometric evaluation.

Objective: Assess the metabolic profile of a pediatric population at a specific age to describe the association between anthropometric and biochemical cardiovascular disease risk factors; and evaluate selected anthropometric variables as potential predictors for dyslipidemic cardiovascular risk.

Design And Methods: Anthropometric features, bioimpedance parameters and fasting clinical profile were assessed in Lisbon and the Tagus Valley region pre-pubertal nine-year-old children (n = 1.496) from 2009-2013 in a descriptive, cross-sectional study. Anthropometric variables predictive power was evaluated through regression analysis.

Results: At least one abnormal lipid parameter was found in 65% of "normal weight", 73% of "overweight" and 81% of "obese" children according to the International Obesity Task Force (IOTF) standards. Dyslipidemia was present in 67.8% of children. Waist-hip ratio (WHR) explained 0.4% of total cholesterol (TC) variance. Waist circumference (WC) explained 2.8% of apolipoprotein (APO) A1 variance. Waist-circumference-to-height-ratio (WHtR) explained 2.7%, 2.8% and 1.9% of low-density lipoprotein cholesterol (LDL-c), APO B, and N_HDL-c variance, respectively. Children with abnormally high WHR levels had an increase in risk of 4.49, 3.40 and 5.30 times, respectively, for developing cardiovascular disease risk factors measured as high-risk levels of TC, LDL-c and non-HDL-c (N_HDL-c) (p<0.05). Only 29.9% of "normal weight" children had no anthropometric, bioimpedance or biochemical parameters associated with CV risk.

Conclusion: A large proportion of school age children have at least one lipid profile abnormality. BMI, zBMI, calf circumference (CC), hip circumference (HC), WC, and WHR are directly associated with dyslipidemia, whereas HC and calf circumference (CC) adjusted to WC, and mid-upper arm circumference (MUAC), are all inversely associated with dyslipidemia. Selected anthropometric variables are likely to help predict increased odds of having CV risk factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983423PMC
December 2018

Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children.

Endocrine 2018 06 20;60(3):466-478. Epub 2018 Apr 20.

Centro de Genética Médica e Nutrição Pediátrica Egas Moniz, Campus Universitário, Monte da Caparica, Portugal.

Purpose: Evaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children.

Research Question: What is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children?

Methods: A cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children.

Results: FTO rs9939609 was associated with an increase in body mass index (BMI) and BMI z-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (P< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (P < 0.05).

Conclusions: We showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.
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http://dx.doi.org/10.1007/s12020-018-1587-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937906PMC
June 2018

Anthropometric predictors of body fat in a large population of 9-year-old school-aged children.

Obes Sci Pract 2016 09 20;2(3):272-281. Epub 2016 Jul 20.

Centro de Genética Médica e Nutrição Pediátrica Egas Moniz Campus Universitário Monte da Caparica Portugal; Instituto Superior de Ciências da Saúde Egas Moniz Campus Universitário Monte da Caparica Portugal.

Objective: To develop and cross-validate predictive models for percentage body fat (%BF) from anthropometric measurements [including BMI -score (zBMI) and calf circumference (CC)] excluding skinfold thickness.

Methods: A descriptive study was carried out in 3,084 pre-pubertal children. Regression models and neural network were developed with %BF measured by Bioelectrical Impedance Analysis (BIA) as the dependent variables and age, sex and anthropometric measurements as independent predictors.

Results: All %BF grade predictive models presented a good global accuracy (≥91.3%) for obesity discrimination. Both overfat/obese and obese prediction models presented respectively good sensitivity (78.6% and 71.0%), specificity (98.0% and 99.2%) and reliability for positive or negative test results (≥82% and ≥96%). For boys, the order of parameters, by relative weight in the predictive model, was zBMI, height, waist-circumference-to-height-ratio (WHtR) squared variable (_Q), age, weight, CC_Q and hip circumference (HC)_Q (adjusted  = 0.847 and RMSE = 2.852); for girls it was zBMI, WHtR_Q, height, age, HC_Q and CC_Q (adjusted  = 0.872 and RMSE = 2.171).

Conclusion: %BF can be graded and predicted with relative accuracy from anthropometric measurements excluding skinfold thickness. Fitness and cross-validation results showed that our multivariable regression model performed better in this population than did some previously published models.
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http://dx.doi.org/10.1002/osp4.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043499PMC
September 2016

Validation of a New Noninvasive Intracranial Pressure Monitoring Method by Direct Comparison with an Invasive Technique.

Acta Neurochir Suppl 2016 ;122:93-6

University of São Paulo, São Paulo, Brazil.

The search for a completely noninvasive intracranial pressure (ICPni) monitoring technique capable of real-time digitalized monitoring is the Holy Grail of brain research. If available, it may facilitate many fundamental questions within the range of ample applications in neurosurgery, neurosciences and translational medicine, from pharmaceutical clinical trials, exercise physiology, and space applications. In this work we compare invasive measurements with noninvasive measurements obtained using the proposed new noninvasive method. Saline was infused into the spinal channel of seven rats to produce ICP changes and the simultaneous acquisition of both methods was performed. The similarity in the invasive and noninvasive methods of ICP monitoring was calculated using Pearson's correlation coefficients (r). Good agreement between measures < r > = 0.8 ± 0.2 with a range 0.28-0.96 was shown.
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http://dx.doi.org/10.1007/978-3-319-22533-3_18DOI Listing
July 2017

Effect of diabetes mellitus type 2 on salivary glucose--a systematic review and meta-analysis of observational studies.

PLoS One 2014 15;9(7):e101706. Epub 2014 Jul 15.

Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal.

Background: Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.

Methods And Findings: We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).

Conclusions: Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098915PMC
March 2015

Clinical response of azithromycin as an adjunct to non-surgical periodontal therapy in smokers.

J Periodontol 2005 Mar;76(3):426-36

Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.

Background: Antibiotic therapy can be used in very specific periodontal treatment situations such as in refractory cases of periodontal disease found to be more prevalent in smokers. This study was designed to determine the efficacy of azithromycin (AZM) when combined with scaling and root planing (SRP) for the treatment of moderate to severe chronic periodontitis in smokers.

Methods: Thirty-one subjects were enrolled into a 6-month randomized, single-masked trial to evaluate clinical, microbial (using benzoyl- DL-arginine naphthylamine [BANA] assay), and gingival crevicular fluid (GCF) pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) levels in response to SRP alone or SRP + AZM. At baseline, patients who smoked > or =1 pack per day of cigarettes who presented with at least five sites with probing depths (PD) of > or =5 mm with bleeding on probing (BOP) were randomized into the test or control groups. At baseline and 3 and 6 months, clinical measurements (probing depth [PD], clinical attachment loss [CAL], and bleeding on probing [BOP]) were performed. GCF bone marker assessment (Ctelopeptide [ICTP] as well as BANA test analyses) were performed at baseline, 14 days, and 3 and 6 months.

Results: The results demonstrated that both groups displayed clinical improvements in PD and CAL that were sustained for 6 months. Using a subject-based analysis, patients treated with SRP + AZM showed enhanced reductions in PD and gains in CAL at moderate (4 to 6 mm) and deep sites (>6 mm) (P <0.05). Furthermore, SRP + AZM resulted in greater reductions in BANA levels compared to SRP alone (P <0.05) while rebounds in BANA levels were noted in control group at the 6-month evaluation. No statistically significant differences between groups on mean BOP and ICTP levels during the course of the study were noted.

Conclusions: The utilization of AZM in combination with SRP improves the efficacy of non-surgical periodontal therapy in reducing probing depth and improving attachment levels in smokers with moderate to advanced attachment loss.
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http://dx.doi.org/10.1902/jop.2005.76.3.426DOI Listing
March 2005

Camelized rabbit-derived VH single-domain intrabodies against Vif strongly neutralize HIV-1 infectivity.

J Mol Biol 2004 Jul;340(3):525-42

URIA - Centro de Patogénese Molecular, Faculdade de Farmácia, Universidade de Lisboa, Lisboa 1649-019, Portugal.

We recently developed a specific single-chain antibody from immunized rabbits to HIV-1 Vif protein that was expressed intracellularly and inhibited reverse transcription and viral replication. The Vif of HIV-1 overcomes the innate antiviral activity of a cytidine deaminase Apobec3G (CEM15) that induces G to A hypermutation in the viral genome, resulting in enhancement of viral replication infectivity. Here, we have developed a minimal scaffold VH fragment with intrabody properties derived from anti-Vif single-chain antibody that was engineered to mimic camelid antibody domains. Non-specific binding of VH by its interface for the light chain variable domain (VL) was prevented through amino acid mutations in framework 2 and 4 (Val37F, G44E, L45R, W47G and W103R). Our results demonstrate that all constructed anti-Vif VH single-domains preserve the antigen-binding activity and specificity in the absence of the parent VL domain. However, only the most highly camelized domains had high levels of intracellular expression. The expression in eukaryotic cells showed that VH single-domains could correctly fold as soluble proteins in the reducing environment. The results demonstrated an excellent correlation between improvements in protein solubility with gradually increasing camelization. Camelized single-domains efficiently bound Vif protein and neutralized its infectivity enhancing function, by reducing late reverse transcripts and proviral integration. The activity of the anti-Vif single-domains was shown to be cell-specific, with inhibitory effects only in cells non-permissive that require Vif for HIV-1 replication. Moreover, cell specificity of anti-Vif intrabodies was correlated with an increase of Apobec3G, which potentiates viral inhibition. The present study strongly suggests that camelization of rabbit VH domains is a potentially useful approach for engineering intrabodies for gene therapy.
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http://dx.doi.org/10.1016/j.jmb.2004.04.062DOI Listing
July 2004

Critical review of immediate implant loading.

Clin Oral Implants Res 2003 Oct;14(5):515-27

Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.

Background: Implant dentistry has become successful with the discovery of the biological properties of titanium. In the original protocol, studies have advocated a 2-stage surgical protocol for load-free and submerged healing to ensure predictable osseointegration. However, the discomfort, inconvenience, and anxiety associated with waiting period remains a challenge to both patients and clinicians. Hence, loading implant right after placement was attempted and has gained popularity among clinicians. Issues/questions related to this approach remain unanswered. Therefore, it is the purpose of this review article to (1). review and analyze critically the current available literature in the field of immediate implant loading and (2). discuss, based on scientific evidence, factors that may influence this treatment modality.

Material And Methods: Literature published over the past 20 years was selected and reviewed. Findings from these studies were discussed and summarized in the tables. The advantages and disadvantages associated with immediate implant loading were analyzed. Factors that may influence the success of immediate implant loading, including patient selection, type of bone quality, required implant length, micro- and macrostructure of the implant, surgical skill, need for achieving primary stability/control of occlusal force, and prosthesis guidelines, were thoroughly reviewed and discussed.

Results And Conclusion: Various studies have demonstrated the feasibility and predictability of this technique. However, most of these articles are based on retrospective data or uncontrolled cases. Randomized, prospective, parallel-armed longitudinal human trials are primarily based on short-term results and long-term follow-ups are still scarce in this field. Nonetheless, from available literature, it may be concluded that anatomic locations, implant designs, and restricted prosthetic guidelines are key to ensure successful outcomes. Future studies, preferably randomized, prospective longitudinal studies, are certainly needed before this approach can be widely used.
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http://dx.doi.org/10.1034/j.1600-0501.2003.00950.xDOI Listing
October 2003

Influence of sex hormones on the periodontium.

J Clin Periodontol 2003 Aug;30(8):671-81

Department of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.

Objectives: Sex hormones have long been considered to play an influential role on periodontal tissues, bone turnover rate, wound healing and periodontal disease progression. The objectives of this review article are to (1) address the link between sex hormones and the periodontium, (2) analyse how these hormones influence the periodontium at different life times and (3) discuss the effects of hormone supplements/replacement on the periodontium.

Materials And Methods: Two autonomous searches were performed in English language utilizing Medline, Premedline and Pubmed as the online databases. Publications up to 2002 were selected and further reviewed. In addition, a manual search was also performed including specific related journals and books.

Results: It is certain that sexual hormones play a key role in periodontal disease progression and wound healing. More specifically, these effects seem to differentiate by gender as well as lifetime period. In addition, the influence of sex hormones can be minimized with good plaque control and with hormone replacement.

Conclusion: Despite profound research linking periodontal condition with sex hormones kinetics, more definitive molecular mechanisms and therapy still remain to be determined.
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http://dx.doi.org/10.1034/j.1600-051x.2003.00055.xDOI Listing
August 2003
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