Retraction Note: The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study.

The article "The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study", by K. Dhuli, C. Micheletti, M.C. Medori, G. Madeo, G. Bonetti, K. Donato, F. Gaffuri, G.M. Tartaglia, S. Michelini, A. Fiorentino, D. Cesarz, S.T. Connelly, N. Capodicasa, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 33-38-DOI: 10.26355/eurrev_202312_34687-PMID: 38112946 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Issues in methodology -       Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors disagree with this retraction. https://www.europeanreview.org/article/34687 This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

SALIVA-based diagnostic approach for diabetes mellitus: a step towards non-invasive detection - a scoping review.

OBJECTIVE: Diabetes mellitus (DM) is a chronic autoimmune disease whose main feature is chronic hyperglycemia. The causes of DM are impaired insulin secretion, impaired insulin action, or both. Saliva is a biofluid that can be considered as a "mirror" reflecting our body's health status; with the rapid advancement in salivaomics, saliva, being a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. As there are no precise guidelines about the salivary biomarkers correlated with the diagnosis of diabetes, a review was conducted to verify whether saliva analysis can be feasible and which biomarkers are more reliable, for the diagnosis of this disease. MATERIALS AND METHODS: A literature search was performed through PubMed, Medline, Scopus, Web of Science, LILACS, Open Grey, and Cochrane Library databases. The "PRISMA" guidelines were used for the following review, and thirty-three studies were analyzed. RESULTS: Almost all salivary glucose studies suggest that the estimation of this biomarker can be used as a potential indicator. Furthermore, studies that considered other biomarkers such as 1,5-anhydroglucitol, alpha-amylase, N-acetyl-ß-D-hexosaminidase, asprosin, resistin, and fructosamine reported that these biomarkers resulted to be potentially useful for diabetes screening and diagnosis, with the exception of the cystatin SA. CONCLUSIONS: In conclusion, several salivary biomarkers could be useful for monitoring DM, but it would be necessary to further expand the research and define precise values for each marker in order to predict with reasonable confidence if an individual is healthy or suffering from diabetes. Finally, standardized saliva collection and processing techniques are key to minimizing interindividual variability in saliva composition.

What is the use of nutraceuticals in dentistry? A scoping review.

OBJECTIVE: Recently, nutraceuticals have been widely explored in many medical fields and their use is also increasing in oral and dental problems. Since the nutraceutical evidence landscape in the literature has not been fully elucidated yet, this review aims to examine the effects of commercially available nutraceuticals and their potential evidence and applications in dentistry. MATERIALS AND METHODS: A scoping review was conducted following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR)" checklist. The electronic search was performed using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science on March 2022. The inclusion criteria include humans, clinical trials, randomized controlled trials (RCT), reviews, and systematic reviews published over the last ten years. RESULTS: 18 studies met the eligibility criteria. There were 2 RCTs, 11 systematic reviews, and four narrative reviews. In most studies, the clinical indications were oral leucoplakia, periodontitis, osseointegration of implants, oral mucositis, oral clefts, and oral health. Probiotics, prebiotics, polyunsaturated fatty acids, and vitamins A, B, C, D, and E were the most common nutraceuticals used in dentistry. CONCLUSIONS: Nutraceuticals are foods that, according to the literature, may be useful for preventing and treating dental diseases.

3D Computed Tomography vs. 2D radiography: comparison of 3D direct anthropometry with 2D norm calculations and analysis of differences in soft tissue measurements.

OBJECTIVE: The aim of this study was twofold: (1) to compare soft tissue measurements of the same distances obtained from 3D computed tomography reconstructions with 2D cephalometric radiograms, (2) to compare data from 3D measurements from direct anthropometry and 2D "norms" for the facial measurements. PATIENTS AND METHODS: A total of 40 Caucasian patients that had their CBCT scans for various dental and dentoskeletal reasons were enrolled in this study. All the patients had large field of view (from the forehead to the chin). The data were stored in DICOM format and imported into a software for 3D reconstructions. After 3D facial soft tissue model generation, the distances between 18 soft tissue points were measured. The 3D soft tissue analysis was performed, and the facial indices were calculated. The mean 3D values were compared with 2D measurements performed on lateral cephalograms and Arnett's and Farkas' norms. The measurements were statistically compared using Student's t-test. RESULTS: Assessments from 2D and 3D measurements showed no statistical difference except for the distance Pogonion (for both male and female) and Labial superius prominence (females) to the True Vertical Line in 2D /Plane in case of 3D measurements. There was a significant difference between all 3D measurements and Arnett's and anthropometric Farkas' "norms". The mean difference between Farkas' "norms" and 3D measurements was within 3 mm for 70% of measurements. CONCLUSIONS: According to the results, 3D soft tissue analysis allows for complete diagnostic determination. The 3D "norms" are to be verified on a greater sample.

Lymphatic circulation in astronauts: basic knowledge, challenges and perspectives.

Space missions expose the astronauts' bodies to various stressors, including microgravity. While numerous studies have investigated the effects of this stressor, research on its impact on the lymphatic system remains confidential. This review highlights the importance of scientific research into the human lymphatic system exposed to long-duration space missions. The safety of astronauts is a major issue. Chronic slowing of lymphatic drainage disrupts the balance of fluid and macromolecule exchange within poorly drained anatomical areas. Their extracellular matrix gradually becomes the site of dispersed deposits of degraded proteins and increased local water content. The interaction between these two phenomena leads to mutual amplification, resulting in a slow, gradual increase in pressure within the impacted tissue, which undergoes an expansion known as edema. The speed at which these pathophysiological processes take hold includes the extent of the lymphatic insufficiency and any compensatory measures that may or may not be put in place. Lymphatics are present everywhere in the body where tissues receive blood. Organs such as the brain, heart, and intestines, among others, as well as local immune function, can be damaged over time when their lymphatic system becomes chronically insufficient. The human clinical experience of lymphatic insufficiency tells us that the onset of edema takes time and is an insidious but inevitable phenomenon if adequate compensation does not occur. The time required for the pathophysiological consequences of lymphatic insufficiency to become established does not coincide with the time allocated to bed rest experiments or current space missions. With the prospect of longer space missions, lymphatic insufficiency linked to microgravity could unexpectedly become a major obstacle to human life in space.

Bioetics Issues of Artificial Placenta and Artificial Womb Technology.

Abstract: The worldwide infertility crisis and the increase in mortality and morbidity among infants, due to preterm births and associated complications, have stimulated research into artificial placenta (AP) and artificial womb (AW) technology as novel solutions. These technologies mimic the natural environment provided in the mother's womb, using chambers that ensure the supply of nutrients to the fetus and disposal of waste substances through an appropriate mechanism. This review aims to highlight the background of AP and AW technologies, revisit their historical development and proposed applications, and discuss challenges and bioethical and moral issues. Further research is required to investigate any negative effects of these new technologies, and ethical concerns pertaining to the structure and operation of this newly developed technology must be addressed and resolved prior to its introduction to the public sphere.

The Role of Olive Tree Polyphenols In The Prevention of COVID-19: A Scoping Review Part 2.

Abstract: The recent COVID-19 pandemic caused by SARS-CoV-2 affected hundreds of millions of people and caused millions of deaths. There are few effective medications against SARS-CoV-2, and several studies attempted to make drugs based on natural components, such as olive leaves. Olive leaves are rich in polyphenolic compounds, which were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. Polyphenols have renown anti-inflammatory and multitarget antiviral effects on several virus families, which could be among the reasons of the beneficial effects of the Mediterranean diet against COVID-19. This scoping review is focused on the effect of olive tree polyphenols as a natural remedy to inhibit SARS-CoV-2, mainly discussing their influence on the process of viral entry into host cells by endocytosis.

The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study.

OBJECTIVE: COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a global pandemic in 2019. Its main symptoms include fever, cough, fatigue, and, in severe cases, pneumonia, acute respiratory distress syndrome, and organ failure, which can be life-threatening. Various therapies have been proposed for treating COVID-19, among which antiviral drugs and monoclonal antibodies, but natural molecules have gained attention for their potential antiviral properties against various viral infections, including COVID-19. The use of hydroxytyrosol (HT), a polyphenol from the olive tree possessing antioxidant, anti-inflammatory, and anti-viral properties, has been proposed to reduce COVID-19 infection. SUBJECTS AND METHODS: A total of 443 subjects were recruited from four centers, located in Albania, Germany, and Italy (Milan and Trento provinces). The participants were randomly assigned to receive either the dietary supplement containing HT or a placebo for a duration of one month. RESULTS: Analysis of the study data revealed that, among the subjects who tested positive for COVID-19 during the study, 36% belonged to the group that received the dietary supplement containing HT, while 64% belonged to the placebo group. The difference was statistically significant. These findings suggest that the use of a dietary supplement containing HT may have a possible preventive effect against COVID-19 infection. CONCLUSIONS: The study's results indicate that the dietary supplement containing HT shows promise as a possible preventive measure against COVID-19 infection. Large-scale, randomized clinical trials and animal studies could be useful to provide more definitive conclusions on HT's possible potential preventive effects against COVID-19, which could potentially supplement existing therapies and contribute to fighting COVID-19 infection.

The Role of Olive Tree Polyphenols in the Prevention of COVID-19: A Scoping Review, part 1.

Abstract: The global COVID-19 outbreak, started in December 2019, resulted in severe financial losses and extraordinary health crises. Finding a potent and secure medication candidate to treat SARS-CoV-2 infection and its symptoms is still an urgent global need. After reviewing previous studies, olive leaves, being rich in polyphenolic compounds (a large class of bioactive substances naturally found in plants), were proposed as a viable co-therapy supplement to treat and improve clinical symptoms in COVID-19 patients. It has long been known that olive tree polyphenols-such as oleuropein, hydroxytyrosol, verbascoside, as well as triterpenoids like maslinic, ursolic, and oleanolic acids-have anti-inflammatory and multitarget antiviral effects on several virus families, and they could be one of the reasons of the beneficial effects of the Mediterranean diet against COVID-19. Thus, olive tree poly-phenols were tested in silico and in vitro for preventing SARS-CoV-2 infection, claiming that they have beneficial effects. Nevertheless, there is still a small number of research studies on this topic. The aim of this scoping review is to provide more information and offer an opinion on the feasibility of using olive tree polyphenols as a springboard for the creation of innovative natural remedies against this viral illness, ultimately planning future relevant studies.

Salivary proteomic profile of young healthy subjects.

Background: The incidence of noncommunicable diseases (NCDs) has been rapidly ramped up worldwide. Hence, there is an urgent need to non-invasively detect NCDs possibly by exploiting saliva as a 'liquid biopsy' to identify biomarkers of the health status. Since, the absence of standardized procedures of collection/analysis and the lack of normal ranges makes the use of saliva still tricky, our purpose was to outline a salivary proteomic profile which features healthy individuals. Methods: We collected saliva samples from 19 young blood donors as reference population and the proteomic profile was investigated through mass-spectrometry. Results: We identified 1,004 proteins of whose 243 proteins were shared by all subjects. By applying a data clustering approach, we found a set of six most representative proteins across all subjects including Coronin-1A, F-actin-capping protein subunit alpha, Immunoglobulin J chain, Prosaposin, 78 kDa glucose-regulated protein and Heat shock 70 kDa protein 1A and 1B. Conclusion: All of these proteins are involved in immune system activation, cellular stress responses, proliferation, and invasion thus suggesting their use as biomarkers in patients with NCDs.

In Memory of Professor Derek Pheby.

Abstract: Professor Derek Pheby's passing in November 2022 marked a profound loss for the scientific community. Professor Derek Pheby, a stalwart figure in the fields of autoimmune diseases and bioethics, was known for his dedication to scientific research and patients' support, particularly for those affected by paraneoplastic autoimmune syndromes. Professor Pheby made significant contributions to research, especially about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). His leadership of the ME Biobank and scientific coordination of EUROMENE demonstrated his commitment to pushing boundaries and fostering international collaborations. Professor Pheby's scientific work addressed various aspects of ME/CFS, from physician education to patient needs, the development of a post-mortem tissue bank, and effective treatments. Beyond his medical career, Professor Pheby was a crucial member of the Independent Ethics Committee of MAGI, he was a poet, humanitarian, and advocate for child protection. His generosity and boundless spirit left an enduring legacy, fostering innovative research in the pursuit of combating autoimmune diseases.

Human Cloning: Biology, Ethics, and Social Implications.

Abstract: This scholarly article delves into the multifaceted domains of human cloning, encompassing its biological underpinnings, ethical dimensions, and broader societal implications. The exposition commences with a succinct historical and contextual overview of human cloning, segueing into an in-depth exploration of its biological intri-cacies. Central to this biological scrutiny is a comprehensive analysis of somatic cell nuclear transfer (SCNT) and its assorted iterations. The accomplishments and discoveries in cloning technology, such as successful animal cloning operations and advances in the efficiency and viability of cloned embryos, are reviewed. Future improvements, such as reprogramming procedures and gene editing technology, are also discussed. The discourse extends to ethical quandaries intrinsic to human cloning, entailing an extensive contemplation of values such as human dignity, autonomy, and safety. Furthermore, the ramifications of human cloning on a societal plane are subjected to scrutiny, with a dedicated emphasis on ramifications encompassing personal identity, kinship connections, and the fundamental notion of maternity. Culminating the analysis is a reiteration of the imperative to develop and govern human cloning technology judiciously and conscientiously. Finally, it discusses several ethical and practical issues, such as safety concerns, the possibility of exploitation, and the erosion of human dignity, and emphasizes the significance of carefully considering these issues.

Myoelectric manifestations of jaw elevator muscle fatigue and recovery in healthy and TMD subjects.

The effects of muscle pain and fatigue on the control of jaw elevator muscles are not well known. Furthermore, the myoelectric manifestations of fatigue and recovery from fatigue in the masticatory muscles are not reported in literature. The main aims of this study were (i) to evaluate the possible use of surface electromyography (sEMG) as an objective measure of fatigue of the jaw elevator muscles, (ii) to compare the myoelectric manifestations of fatigue in the temporalis anterior and masseter muscles bilaterally, (iii) to assess recovery of the investigated muscles after an endurance test and (iv) to compare fatigue and recovery of the jaw elevator muscles in healthy subjects and patients with muscle-related temporomandibular disorders (TMD). The study was performed on twenty healthy volunteers and eighteen patients with muscle-related TMD. An intra-oral compressive-force sensor was used to measure the voluntary contraction forces close to the intercuspal position and to provide visual feedback of submaximal forces to the subject. Surface EMG signals were recorded with linear electrode arrays during isometric contractions at 20%, 40%, 60% and 80% of the maximum voluntary contraction force, during an endurance test and during the recovery phase. The results showed that (i) the slope of the mean power spectral frequency (MNF) and the initial average rectified value (ARV) could be used to monitor fatigue of the jaw elevators, (ii) the temporalis anterior and masseter muscle show the same myoelectric manifestations of fatigue and recovery and (iii) the initial values of MNF and ARV were lower in patients with muscle-related TMD. The assessment of myoelectric manifestations of fatigue in the masticatory muscles may assist in the clinical assessment of TMDs.

Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies.

OBJECTIVE: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. MATERIALS AND METHODS: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. RESULTS: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. CONCLUSIONS: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.

In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This virus attacks cells of the airway epithelium by binding transmembrane angiotensin-converting enzyme 2 (ACE2). Hydroxytyrosol has anti-viral properties. Alpha-cyclodextrin can deplete sphingolipids and phospholipids from cell membranes. The aim of the present experimental study was to evaluate the efficacy of α-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2 infection in in vitro cell models and humans. PATIENTS AND METHODS: For in vitro experiments on Vero E6 cells, RNA for RT-qPCR analysis was extracted from Caco2 and human fibroblast cell lines. For study in humans, the treatment group consisted of 149 healthy volunteers in Northern Cyprus, considered at higher risk of SARS-CoV-2 infection than the general population. The volunteers used nasal spray containing α-cyclodextrin and hydroxytyrosol for 4 weeks. The control group consisted of 76 healthy volunteers who did not use the spray. RESULTS: RT-qPCR experiments on targeted genes involved in endocytosis showed a reduction in gene expression, whereas cytotoxicity and cytoprotective tests showed that the compounds exerted a protective effect against SARS-CoV-2 infection at non-cytotoxic concentrations. None of the volunteers became positive to SARS-CoV-2 RT-qPCR assay during the 30 days of treatment. CONCLUSIONS: Treatment with α-cyclodextrin and hydroxytyrosol nasal spray improved defenses against SARS-CoV-2 infection and reduced synthesis of viral particles.

Electromyographic standardized indices in healthy Brazilian young adults and data reproducibility.

The determination of normal parameters is an important procedure in the evaluation of the stomatognathic system. We used the surface electromyography standardization protocol described by Ferrario et al. (J Oral Rehabil. 2000;27:33-40, 2006;33:341) to determine reference values of the electromyographic standardized indices for the assessment of muscular symmetry (left and right side, percentage overlapping coefficient, POC), potential lateral displacing components (unbalanced contractile activities of contralateral masseter and temporalis muscles, TC), relative activity (most prevalent pair of masticatory muscles, ATTIV) and total activity (integrated areas of the electromyographic potentials over time, IMPACT) in healthy Brazilian young adults, and the relevant data reproducibility. Electromyography of the right and left masseter and temporalis muscles was performed during maximum teeth clenching in 20 healthy subjects (10 women and 10 men, mean age 23 years, s.d. 3), free from periodontal problems, temporomandibular disorders, oro-facial myofunctional disorder, and with full permanent dentition (28 teeth at least). Data reproducibility was computed for 75% of the sample. The values obtained were POC Temporal (88.11 +/- 1.45%), POC masseter (87.11 +/- 1.60%), TC (8.79 +/- 1.20%), ATTIV (-0.33 +/- 9.65%) and IMPACT (110.40 +/- 23.69 microV/microV.s %). There were no statistical differences between test and retest values (P > 0.05). The Technical Errors of Measurement (TEM) for 50% of subjects assessed during the same session were 1.5, 1.39, 1.06, 3.83 and 10.04. For 25% of the subjects assessed after a 6-month interval, the TEM were 0.80, 1.03, 0.73, 12.70 and 19.10. For all indices, there was good reproducibility. These electromyographic indices could be used in the assessment of patients with stomatognathic dysfunction.

A therapeutic dose of FK506 does not affect collagen turnover pathways in healthy human gingival fibroblasts.

We previously demonstrated that a high dose of tacrolimus (1 mumol/L) induced expression of matrix metalloproteinase (MMP) proteins in human cultured gingival fibroblasts, suggesting a molecular mechanism maintaining gingival collagen homeostasis in tacrolimus-treated patients. Herein we have analyzed whether the effect on collagen turnover might be influenced by a therapeutic tacrolimus dose. Human gingival fibroblasts were incubated for 72 hours with 10 nmol/L, 100 nmol/L, and 1 mumol/L tacrolimus, or left untreated (CT). Collagen type I and III (COL-I, COL-III), lysyl hydroxylase 2b (LH2b), MMP-1 and -2, tissue inhibitor of MMP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA levels were assayed by reverse-transcriptase polymerase chain reaction, collagen protein levels by dot blot, and MMP activity by sodium dodecyl sulfate zymography. Tacrolimus did not affect COL-I, COL-III, or MMP gene expression, while LH2b and TGF-beta1 tended to be down-regulated after 1 mumol/L FK506. Conversely, protein levels of MMP-1 (P = NS) and MMP-2 (P < .05 vs CT, 10 nmol/L, 100 nmol/L) were up-regulated after 1 mumol/L tacrolimus. Our findings confirmed that a high dose of tacrolimus does not induce interstitial collagen overexpression by gingival fibroblasts and induces up-regulation of MMPs protein levels. Interestingly, at doses corresponding to whole blood trough levels, tacrolimus did not exert any evident effect on collagen turnover pathways, suggesting that tacrolimus is likely to not affect collagen homeostasis in the gingival connective tissue compartment of FK506-immunosuppressed subjects. This effect did not seem to be dose-dependent.

Clinical outcomes of Botox injections for chronic temporomandibular disorders: do we understand how Botox works on muscle, pain, and the brain?

The main objective of this retrospective review was to analyze the clinical outcomes following the use of botulinum toxin (onabotulinumtoxinA, Botox) injections to relieve the symptoms of chronic temporomandibular disorders (TMD). Seventy-one patients with a diagnosis of TMD (according to the RDC/TMD international consortium) associated with or without bruxism and refractory to conventional treatment (e.g. oral appliances, physiotherapy, etc.) received Botox injections into the temporalis and masseter muscles. Subjective responses to Botox were categorized as 'beneficial' or 'not beneficial', as patient-reported outcomes based on the subjective reduction in pain and/or improvement in function. Fifty-five of the 71 subjects (77%) reported beneficial effects with Botox. Subjects with a concomitant bruxism diagnosis reported significant improvement over subjects without bruxism (87% vs. 67%; P=0.042). Subjects with stress-related psychiatric comorbidities and bruxism had a significantly higher benefit than those with stress-related psychiatric comorbidities alone (P=0.027). Patients reported less improvement if the time between the initial Botox injection and follow-up was less than an average of 5 weeks, compared to an average follow-up of 5-10 weeks (P=0.009). The subgroup TMD diagnosis and time interval post-injection are important predictors of patient-reported beneficial outcomes.

Morphometry of the ear in Down's syndrome subjects. A three-dimensional computerized assessment.

The three-dimensional coordinates of 13 soft-tissue landmarks on the ears were obtained by a computerized digitizer in 28 subjects with Down's syndrome aged 12-45 years, and in 449 sex, age and ethnic group matched controls. From the landmarks, left and right linear distances (ear width and length), ratios (ear width-to-ear length), areas (ear area), angles (angle of the auricle versus the facial midplane) and the three-dimensional symmetry index were calculated. For both males and females, all linear dimensions and areas were significantly (Analysis of Variance, P < 0.001) larger in the reference subjects than in the subjects with Down's syndrome. All values significantly increased as a function of age (P < 0.05); the increment was larger in the reference subjects than in the subjects with Down's syndrome. On both sides of the face, the subjects with Down's syndrome had larger ear width-to-ear length ratios, and larger angles of the auricle versus the facial midplane than the reference subjects. The three-dimensional symmetry index was significantly larger in the reference subjects and in the older persons. In conclusion, ear dimensions, position and shape significantly differed in subjects with Down's syndrome when compared to sex, age and ethnic group matched controls. Some of the differences were sex and age related.