Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients

BACKGROUND: The association between lesion type, disease stage and severity of pain was studied in a large group of women with endometriosis to verify whether endometrial implants at different sites determine specific complaints and to evaluate the validity of the current classification system in women with symptomatic disease. METHODS: A total of 1054 consecutive women with endometriosis undergoing first-line conservative or definitive surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, and type and severity of pain symptoms were collected and analysed by multiple logistic regression. RESULTS: Minimal endometriosis was present in 319 patients, mild in 139, moderate in 292 and severe in 304. A significant inverse relationship was demonstrated between age at surgery and moderate-to-severe dysmenorrhoea, dyspareunia and non-menstrual pain. A strong association was found between posterior cul-de-sac lesions and pain at intercourse [Wald chi (2) = 17.00, P = 0.0001; odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.68-4.24]. A correlation between endometriosis stage and severity of symptoms was observed only for dysmenorrhoea (Wald chi (2) = 5.14, P = 0.02) and non-menstrual pain (Wald chi (2) = 5.63, P = 0.018). However, the point estimates of ORs were very close to unity (respectively, 1.33, 95% CI = 1.04-1.71, and 1.01, 95% CI = 1.00-1.03). CONCLUSIONS: The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power.     

An algorithm for the recovery of fetal heart rate series from CTG data

Cardiotocography (simultaneous recording of fetal heart rate (FHR) and uterine contractions) is one of the most used diagnostic techniques to evaluate fetal well-being and to investigate the functional state of the fetal autonomic nervous system. Recently, great interest has been paid to the variability of the FHR, and its frequency analysis, as a base for a more objective analysis of the cardiotocographic (CTG) tracings. FHR signals are unevenly sampled series. To obtain evenly sampled series, cardiotocographs often use zero-order interpolation. Such process is simple and fast but results unsuitable for frequency analyses because it introduces alterations in the FHR power spectrum. An algorithm for the recovery of the true FHR series out of the zero-order interpolated CTG data was developed and evaluated.     

Erythema multiforme and related disorders

Erythema multiforme (EM) and related disorders comprise a group of mucocutaneous disorders characterized by variable degrees of mucosal and cutaneous blistering and ulceration that occasionally can give rise to systemic upset and possibly compromise life. The clinical classification of these disorders has often been variable, thus making definitive diagnosis sometimes difficult. Despite being often caused by, or at least associated with, infection or drug therapy, the pathogenic mechanisms of these disorders remain unclear, and as a consequence, there are no evidence-based, reliably effective therapies. The present article reviews aspects of EM and related disorders of relevance to oral medicine clinical practice and highlights the associated potential etiologic agents, pathogenic mechanisms and therapies.     

High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.     

Qualitative and quantitative evaluation of mitral valve morphology by intraoperative volume-rendered three-dimensional echocardiography

BACKGROUND AND AIM OF THE STUDY: Two-dimensional echocardiography (2DE) performed to evaluate mitral valve anatomy during valve repair has certain limitations and pitfalls. The study aim was to assess the feasibility, accuracy and incremental value of three-dimensional echocardiography (3DE), coupled with 2DE in evaluating mitral valve structure, before and after repair and pericardial posterior annuloplasty. METHODS: The site and extent of mitral valve prolapse, systolic and diastolic changes of mitral annular area were evaluated using 2D and 3D transesophageal echocardiography (TEE), both pre- and postoperatively in 34 patients before and after mitral valve repair and pericardial posterior annuloplasty. RESULTS: Concordance between 2DE and surgery in evaluating prolapsing mitral valve scallops was 76% for the anterior leaflet and 75% for the posterior leaflet; for 3DE and surgery, concordance was 87% and 93% respectively. There was a significant reduction in maximal and minimal annular area after surgery, with a statistically significant difference between systolic-diastolic changes. CONCLUSION: 3DE, coupled with 2DE, is feasible and accurate in delineating the extent and location of prolapsing scallops of the mitral valve. The combined approach is also valuable in planning mitral valve surgery and evaluating the mitral valve annulus in vivo.     

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group. In the current study, we assessed potential toxicity mechanisms in the lanthanide series using a functional toxicogenomics approach in baker’s yeast, which shares many cellular pathways and functions with humans. We screened the homozygous deletion pool of 4,291 Saccharomyces cerevisiae strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein–protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.

Since their discovery, lanthanides have presented both difficulty and opportunity for researchers. As a series, these elements behave rather similarly: most of them form +3 ions in aqueous solution (1), prefer highly electronegative anionic ligands (2), and form insoluble hydroxide precipitates at neutral pH if not otherwise complexed (3). Although the chemical similarities between these elements made their initial isolation and characterization a significant challenge, they now have unique applications in industry and medicine. Several lanthanides have become critical materials for many clean and sustainable energy technologies that will drive the future of our societies and are used, for example, in the production of batteries, magnets, motors, and other electronic components (4); low-concentration mixtures of lanthanides are used in Chinese agriculture to increase body weight gain among livestock (5, 6); lanthanum carbonate (sold under the commercial name of Fosrenol) is a noncalcium phosphate binder used to control hyperphosphataemia (7); and gadolinium is employed in diagnostic medicine, as an essential component of MRI contrast agents (8, 9).The growing use of lanthanides has increased the potential for human exposure to large concentrations of these metals, requiring more detailed investigations into their toxicological properties. For instance, administration of gadolinium-based contrast agents has been associated with the development of nephrogenic systemic fibrosis in patients with compromised renal function (10–12). Moreover, accumulation of gadolinium in the brains of patients who received repeated doses of gadolinium-based contrast agents has also been reported (13). Despite the current ubiquity of lanthanides, their toxicological profile has been incompletely characterized because until recently they were considered to be of low toxicological concern (14, 15). Previous toxicity studies primarily focused on lanthanum or cerium (and, to a lesser extent, neodymium and gadolinium), with the notion that these metals were representative of the series (14, 16–18). However, to our knowledge, no comprehensive mechanistic assay has been conducted to evaluate metal toxicity across the series, and little is known about what toxicological mechanisms may be shared by the different lanthanides.Saccharomyces cerevisiae is one of the best-characterized model organisms (19, 20), and there are many tools available for analyzing its genomic data (21–23). For example, yeast functional toxicogenomic screening is a powerful tool for investigating cellular mechanisms of cytotoxicity (24, 25). This method makes use of the yeast deletion libraries generated by the Yeast Deletion Project (26), a consortium of researchers across the United States and Canada, to establish relationships between genes and chemical exposures. Researchers used heterozygous and homozygous deletion pools of barcoded yeast strains to derive mechanistic toxicological information about a wide array of chemicals, pharmaceuticals, metals, and biological compounds (27, 28). As eukaryotes, yeast and humans share many cellular pathways and functions, and many components of cell biology identified in S. cerevisiae have homologs in human biology (29–31). Consequently, functional toxicogenomic screening offers unique opportunities to evaluate the mechanisms of cytotoxicity and general biological activity across the lanthanide series in yeast and explore potentially conserved mechanisms in humans.Here, we identify fundamental cellular functions disrupted by lanthanides using functional toxicogenomics in S. cerevisiae. The metals studied had distinct behaviors: early lanthanides showed limited unique functional effects, while middle and late lanthanides had prominent and distinct ones. Although the functional effects of each lanthanide were different and suggested some very efficient element discrimination by endogenous molecules, we observed a few common trends. In particular, vesicle-mediated transport (primarily endocytosis) was perturbed by the majority of the lanthanides tested. Moreover, protein–protein network analysis suggested that lanthanides mimic calcium ions, interacting with calcium-binding proteins and disrupting processes regulated by this cation. Finally, several of the highly interconnected proteins targeted by multiple lanthanides in the network analysis are conserved in humans, suggesting their roles in the origin of the human health issues associated with lanthanide exposure and opening many directions for the determination of mechanisms associated with toxicity.     

Methods for measurement of root canal curvature: a systematic and critical review

The assessment of root canal curvature is essential for clinical and research purposes. This systematic review presents an overview of the published techniques for the measurement of root canal curvature features using imaging and to provide a critique of their clinical application. A database search in PubMed, PubMed Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual Health Library was conducted, using appropriate key words to identify measurement methods for root canal curvatures. The search strategy retrieved 10594 records in total, and 31 records fulfilled the inclusion criteria. From 2D image acquisitions, eleven studies measured exclusively the angle of curvature, an additional thirteen measured other curvature features (level, height, radius, length and shape). Seven reports described methods from 3D imaging (CBCT, μCT). Root canal curvatures should be measured, for clinical proposes, to facilitate endodontic treatment planning, and in research, to reduce the risk of selection bias. This review has revealed that there are many methods described in the literature; however, no consensus exists on which method should be used. Some of the methodologies have potential clinical translation, whereas others are suitable for research purpose only, as they require a specific software or radiographic exposure in the mesiodistal direction.     

Inter-Organizational Collaboration in the Implementation of Evidence-based Practices Among Public Agencies Serving Abused and Neglected Youth

This study examined the role of inter-organizational collaboration in implementing new evidence-based practices for addressing problem behaviors in at-risk youth. Semi-structured interviews were conducted with 38 systems leaders of probation, mental health, and child welfare departments of 12 California counties participating in a large randomized controlled trial to scale-up the use of Multidimensional Treatment Foster Care. Three sets of collaboration characteristics were identified: (1) characteristics of collaboration process, (2) characteristics of the external environment, and (3) characteristics of participating organizations and individuals. Inter-organizational collaboration enables an exchange of information and advice and a pooling of resources individual agencies may require for successful implementation.