Predictability and Inducibility of Detachment of Prostatic Central Gland Tissue after Prostatic Artery Embolization: Post Hoc Analysis of a Randomized Controlled Trial

Purpose

To assess the frequency and potential predictors of prostatic central gland tissue detachment (CGD), an enucleation-like reaction that sporadically occurred in a randomized controlled trial assessing efficacy and safety of prostatic artery embolization (PAE).

Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic

Since March 2020, the COVID-19 pandemic has led to the need to re-think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function-preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re-deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions.     

Phylogenomics with paralogs

Phylogenomics heavily relies on well-curated sequence data sets that comprise, for each gene, exclusively 1:1 orthologos. Paralogs are treated as a dangerous nuisance that has to be detected and removed. We show here that this severe restriction of the data sets is not necessary. Building upon recent advances in mathematical phylogenetics, we demonstrate that gene duplications convey meaningful phylogenetic information and allow the inference of plausible phylogenetic trees, provided orthologs and paralogs can be distinguished with a degree of certainty. Starting from tree-free estimates of orthology, cograph editing can sufficiently reduce the noise to find correct event-annotated gene trees. The information of gene trees can then directly be translated into constraints on the species trees. Although the resolution is very poor for individual gene families, we show that genome-wide data sets are sufficient to generate fully resolved phylogenetic trees, even in the presence of horizontal gene transfer.Molecular phylogenetics is primarily concerned with the reconstruction of evolutionary relationships between species based on sequence information. To this end, alignments of protein or DNA sequences are used, whose evolutionary history is believed to be congruent to that of the respective species. This property can be ensured most easily in the absence of gene duplications and horizontal gene transfer (HGT). Phylogenetic studies judiciously select families of genes that rarely exhibit duplications (such as rRNAs, most ribosomal proteins, and many of the housekeeping enzymes). In phylogenomics, elaborate automatic pipelines such as HaMStR (1), are used to filter genome-wide data sets to at least deplete sequences with detectable paralogs (homologs in the same species).In the presence of gene duplications, however, it becomes necessary to distinguish between the evolutionary history of genes (gene trees) and the evolutionary history of the species (species trees) in which these genes reside. Leaves of a gene tree represent genes. Their inner nodes represent two kinds of evolutionary events, namely the duplication of genes within a genome—giving rise to paralogs—and speciations, in which the ancestral gene complement is transmitted to two daughter lineages. Two genes are (co)orthologous if their last common ancestor in the gene tree represents a speciation event, whereas they are paralogous if their last common ancestor is a duplication event; see refs. 2 and 3 for a more recent discussion on orthology and paralogy relationships. Speciation events, in turn, define the inner vertices of a species tree. However, they depend on both the gene and the species phylogeny, as well as the reconciliation between the two. The latter identifies speciation vertices in the gene tree with a particular speciation event in the species tree and places the gene duplication events on the edges of the species tree. Intriguingly, it is nevertheless possible in practice to distinguish orthologs with acceptable accuracy without constructing either gene or species trees (4). Many tools of this type have become available over the last decade; see refs. 5 and 6 for a recent review. The output of such methods is an estimate Θ of the true orthology relation Θ^?, which can be interpreted as a graph G_Θ whose vertices are genes and whose edges connect estimated (co)orthologs.Recent advances in mathematical phylogenetics suggest that the estimated orthology relation Θ contains information on the structure of the species tree. To make this connection, we combine here three abstract mathematical results that are made precise in Materials and Methods below.

• i)Building upon the theory of symbolic ultrametrics (7), we showed that in the absence of horizontal gene transfer, the orthology relation of each gene family is a cograph (8). Cographs can be generated from the single-vertex graph K₁ by complementation and disjoint union (9). This special structure of cographs imposes very strong constraints that can be used to reduce the noise and inaccuracies of empirical estimates of orthology from pairwise sequence comparison. To this end, the initial estimate of G_Θ is modified to the closest correct orthology relation G_Θ^? in such a way that a minimal number of edges (i.e., orthology assignments) are introduced or removed. This amounts to solving the cograph-editing problem (10, 11).
• ii)It is well known that each cograph is equivalently represented by its cotree (9). The cotree is easily computed for a given cograph. In our context, the cotree of G_Θ^? is an incompletely resolved event-labeled gene tree. That is, in addition to the tree topology, we know for each internal branch point whether it corresponds to a speciation or a duplication event. Even though adjacent speciations or adjacent duplications cannot be resolved, the tree faithfully encodes the relative order of any pair of duplication and speciation (8). In the presence of horizontal gene transfer, G_Θ may deviate from the structural requirements of a cograph. Still, the situation can be described in terms of edge-colored graphs whose subgraphs are cographs (7, 8), so that the cograph structure remains an acceptable approximation.
• iii)Every triple (rooted binary tree on three leaves) in the cotree that has leaves from three species and is rooted in a speciation event also appears in the underlying species tree (12). Thus, the estimated orthology relation, after editing to a cograph and conversion to the equivalent event-labeled gene tree, provides much information on the species tree. This result allows us to collect, from the cotrees for each gene family, partial information on the underlying species tree. Interestingly, only gene families that harbor duplications, and thus have a nontrivial cotree, are informative. If no paralogs exist, then the orthology relation G_Θ is a clique (i.e., every family member is orthologous to every other family member) and the corresponding cotree is completely unresolved, and hence contains no triple. On the other hand, full resolution of the species tree is guaranteed if at least one duplication event between any two adjacent speciations is observable. The achievable resolution therefore depends on the frequency of gene duplications and the number of gene families.

Despite the variance reduction due to cograph editing, noise in the data, as well as the occasional introduction of contradictory triples as a consequence of horizontal gene transfer, is unavoidable. The species triples collected from the individual gene families thus will not always be congruent. A conceptually elegant way to deal with such potentially conflicting information is provided by the theory of supertrees in the form of the largest set of consistent triples (13, 14). The data will not always contain a sufficient set of duplication events to achieve full resolution. To this end, we consider trees with the property that the contraction of any edge leads to the loss of an input triple. There may be exponentially many alternative trees of this type. They can be listed efficiently using Semple’s algorithms (15). To reduce the solution space further, we search for a least resolved tree in the sense of ref. 16, i.e., a tree that has the minimum number of inner vertices. It constitutes one of the best estimates of the phylogeny without pretending a higher resolution than actually supported by the data. In SI Appendix, we discuss alternative choices.The mathematical reasoning summarized above, outlined in Materials and Methods, and presented in full detail in SI Appendix, directly translates into a computational workflow, Fig. 1. It entails three NP-hard combinatorial optimization problems: cograph editing (11), maximal consistent triple set (17–19), and least resolved supertree (16). We show here that they are nevertheless tractable in practice by formulating them as Integer Linear Programs (ILP) that can be solved for both artificial benchmark data sets and real-life data sets, comprising genome-scale protein sets for dozens of species, even in the presence of horizontal gene transfer.Open in a separate windowFig. 1.Outline of the computational framework. Starting from an estimated orthology relation Θ, its graph representation G_Θ is edited to obtain the closest cograph G_Θ^*, which, in turn, is equivalent to a (not necessarily fully resolved) gene tree T and an event labeling t. From (T, t), we extract the set ?? of all relevant species triples. As the triple set ?? need not be consistent, we compute the maximal consistent subset ??^? of ??. Finally, we construct a least resolved species tree from ??^?.     

Secondary caries in crowned teeth: correlation of clinical and radiographic findings

STATEMENT OF PROBLEM: The diagnostic value of radiographs for interproximal caries detection on nonrestored teeth is well investigated. However, little is known about the use of radiographs in the diagnosis of secondary caries localized at crown margins. PURPOSE: The aim of this study was to correlate clinical findings with regard to secondary caries with the findings of a radiographic evaluation. MATERIALS AND METHODS: One hundred randomly selected patients who underwent restorations with fixed prostheses and were exhibiting at least one secondary carious lesion were included in the study. A total of 820 restorations (test group, 730 interproximal surfaces of 365 single crowns and 910 interproximal surfaces of 455 fixed partial denture retainer crowns) and 1024 interproximal surfaces of 512 nonrestored teeth (control group) were investigated clinically, with the use of modified California Dental Association criteria, and radiographically for interproximal carious lesions. The extension of the lesions was rated to be initial (with no cavitation), early (with cavitation limited to orthodentin), or deep (with cavitation). The data were statistically analyzed for normal distribution, and the frequency of the findings was calculated in absolute numbers and as a percentage. Statistically significant differences were determined by use of the chi(2) test (P<.05). A linear regression model was applied for the correlation between the percentage of secondary caries and the duration of the crowns in situ. RESULTS: Secondary caries was diagnosed clinically in 11.2% of 1640 interproximal surfaces but only in 8.3% radiographically. In contrast, the frequency of interproximal carious lesions diagnosed clinically in nonrestored teeth increased with the use of radiographs from 3.3% to 4.1%. CONCLUSION: Within the limits of this study, the results confirm that radiographs improve the diagnostic sensitivity for interproximal caries in nonrestored teeth. However, for the diagnosis of secondary caries in crowned teeth, the clinical examination is more reliable than the radiographic evaluation.     

Functional and aesthetic treatment outcomes after immediate jaw reconstruction using a fibula flap and dental implants

Purpose

Microvascular fibula flap surgery is a reliable and effective procedure for reconstructing the jaws after tumour surgery. This procedure allows the placement of dental implants after bone consolidation. This study was designed to evaluate the oral, functional, and aesthetic rehabilitation of tumour patients with immediate fibula transfer and dental implants and included assessment of diet, speech, and aesthetics.

Embolia cutis medicamentosa (Nicolau syndrome) after endodontic treatment: a case report

Introduction

Embolia cutis medicamentosa (Nicolau syndrome) is a rare iatrogenic event of tissue necrosis after intramuscular or intraarticular application of cristalloid suspensions. Clinically, it presents as a livid discoloration of the skin, local pain, and signs of inflammation.

Methods

This article presents the first case of Nicolau syndrome after the endodontic application of calcium hydroxide paste into the distal root canal of tooth 18. The patient presented to the Department for Maxillofacial Surgery and hospitalized for several days.

Results

The application of calcium hydroxide paste led to a thrombosis of the inferior alveolar artery and various branches of the maxillary artery. A definite necrosis of the left-side infraorbital skin area and concomitant hypaesthesia of the infraorbital nerve and of the mental nerve were observed.

Conclusions

Calcium hydroxide paste is appropriate for the medicamentous treatment of root canals, but is not suitable to stanch bleeding from periapical arteries.     

Voids and interlayer gaps in Class 1 posterior composite restorations: a comparison between a microlayer and a 2-layer technique.

OBJECTIVE: The main objective was to compare the presence of interlayer gaps between 2 hybrid composites placed using a microlayer and a 2-layer technique. METHOD AND MATERIALS: Standardized Class 1 cavities were prepared in 40 extracted posterior teeth. Two resin composite materials were used. The control group, group A, consisted of samples of the materials extruded out of the manufacturers' syringes. Group B consisted of 10 teeth restored using 2 layers per restoration. Group C consisted of 30 teeth restored using 6 microlayers per restoration. A scanning electron microscope was used to detect voids in the samples. RESULTS: Round, well-defined voids were found in 85% to 100% of the samples within the bulks of the resin composite materials only. A statistically significant relationship between the type of composite and presence of bubbles (Fisher exact test, P = .04) was found among the 2-layer technique group. No statistically significant difference (Fisher exact test, P = .48) was found among the microlayer technique group. Irregular interlayer gaps were found in 5% to 15% of specimens within areas between bulks of composite, as detected by an electron microscope based on the different densities of the bulks of composite and the interlayer areas. No such statistically significant relationship was found (Fisher exact, P = .62) among the study groups. CONCLUSIONS: Voids are routinely found in bulks of composite materials. Higher incidences of interlayer gaps in the 2-layer samples suggest that the use of a microlayering technique may result in fewer gaps.