Assessment of facial landmarks for bone asymmetry in geometric morphometric studies: A review

BackgroundAnthropometrical points or landmarks are key for facial shape analysis using geometric morphometrics. In the early 1990s Fred Bookstein created a classification system with landmarks type 1., type 2., type 3. based on anatomical landmark homology. However, thirty years later, a uniform referece index of landmarks that can be used for assessing facial asymmetry still does not exist. The criteria for selecting landmark points are not fully defined, which makes classification of homology and and landmarks prone to arbitrary interpretations. A systematic review of literature indicates that authors of studies do not provide explanation for choosing exact points. Most of them also do not provide a clear definition of landmarks and landmarks classification according to homology.ObjectiveThe objective of this systematic review was to assess, in an evidence based manner, which landmarks inside the Bookstein groups of on facial hard tissues can be reccomended for facial asymmetry assessment using geometric mophometrics.Search methodsAn electronic search of 9 databases up to March 2020 by two reviewers was conducted to identify relevant articles.Selection criteriaProspective randomized, non-randomized controlled trials and cross sectional studies reporting on facial asymmetry using three-dimensional images and geometric morphometric methods. The reasons for assessing facial asymmetry were not considered.Data collection and analysisThe 23 selected studies were categorized according to the number and specification of the research subjects, types of three-dimensional images, number of landmarks, and the craniofacial region of interest. All landmarks were extracted with the following data: name, abbreviation, and the author’s definition of the location.ResultsThe craniofacial region is divided into neurobasic cranial part, ethmomaxillar part and the mandible. Assessment of neurobasic cranial asymmetry was conducted in 6 studies and 45 different landmarks were recorded, of which 11 were medial and 34 bilateral. Bregma and Lambda occur most frequently and according to homology both belong to type 1 landmarks.Assessment of ethmomaxillary asymmetry was conducted in 21 studies and 68 different landmarks were recorded, of which 16 were medial and 52 bilateral. Nasion and Jugale occur most frequently and according to homology Nasion belongs to type 1 landmarks and Jugale to type 2 landmarks. Conclusion The selection and definition of craniofacial hard tissue landmarks is one of the most important tasks in the design of morphometric studies, and thus for the purpose of assessing facial asymmetry. The review provides an extensive cross-section of possible landmarks with the definition of the location as well as the possible location variation. The list of these landmarks should be observed through the classification of landmarks according to their homology, as well as possible variations of the classification

Implant Failure: Regional versus Cumulative Evaluation

In this paper the success rate of implant therapy in various bone regions is discussed. The objective is to determine whether differences existed in success rates of cylinder implants placed in different areas in the both maxilla and mandible. Forty four patients have been treated and reviewed five years after the placement of the fixed prosthetic restoration. The patients were provided with a total of 92 implants. Results from this study show very low survival rate for implants placed in anterior region of maxilla (55.6%) after five years. It is concluded that simple cumulative follow up studies do not entirely correspond to actual situations, positioning the implants has an important role in the planning of the implant therapy and that important factor for force compensation is not only the surrounding bone density, but also the region of the jaw where the implants are placed

Orofacial Analysis on the Adriatic Islands: 1. The Island of Hvar as a Model for Odontogenetic Researches

This paper presents a preliminary orofacial analysis of a subadult population of Hvar, a Croatian island in the Adriatic. Its population represents one of the last genetic isolates in Europe and has therefore been the object of intensive crossdisciplinary research over the last 30 years.We focussed on the coefficient of endogamy on the one hand and malocclusal-related caries on the other hand, and expected differences in the latter between subgroups of the population. We analyzed 224 dental casts from children all over the island and found multiple caries in approximal surfaces in 55 percent of the children, but no significant differences between the subpopulations. Instead, significantly more caries affection was found in the boys than in the girls. The percentage of general caries affection is fairly high, even when compared to other isolated populations; it may be due to environmental influence. This would be consistent with the other results, which have putatively been caused by complex environmental influences and not solely by genetic components

Multivariate discovery and replication of five novel loci associated with Immunoglobulin G <i>N</i>-glycosylation

Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes

IgG glycosylation and DNA methylation are interconnected with smoking

Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation

Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury

IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes

Aims/Hypothesis:Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes. Methods: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors. Results: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex. Conclusions: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.</p

Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases.

Funder: FP7 Ideas: European Research Council; Grant(s): 278535, 305280, 324400, 315997The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD

Baseline IgG-Fc N-glycosylation profile is associated with long-term outcome in a cohort of early inflammatory arthritis patients

ackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort.MethodsSera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 ResultsWe observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect −0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model.ConclusionPending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.Proteomic