Protocolo biodigital aplicado al tratamiento de Ortodoncia con alineadores: caso clínico / Biodigital protocol applied to orthodontic treatment with aligners: a clinical case

En la actualidad, contamos con softwares de diseño que nos permiten planificaciones precisas y eficientes de nuestros tratamientos; por lo tanto, nuestros diagnósticos deben estar a la altura. En este artículo presentaremos un caso clínico que se ha desarrollado en el marco de la Diplomatura en Ortodoncia con Alineadores de la Sociedad Argentina Ortodoncia (SAO), donde trabajamos cada pieza dentaria de manera independiente, mediante la técnica de Ortodoncia con alineadores. Teniendo en cuenta que contamos con un stock óseo reducido, utilizamos como aliado un gran recurso: la tomografía computada de haz cónico (CBCT). Esta nos garantiza trabajar con seguridad en casos donde las limitaciones óseas nos dificultan los movimientos dentarios.

We currently find design softwares that allows us to plan our treatments accurately and efficiently; therefore, our diagnoses must be up to par. In this article we will present a clinical case that has been developed within the framework of the Subspeciality in Orthodontics with Aligners Argentine Society of Orthodontics (SAO), where we work, through the orthodontic technique with aligners, each tooth independently. Considering that we have a reduced bone stock, we use as an ally a great resource, the cone beam computed tomography (CBCT), which guarantees us to work safely in these cases where bone limitations hinder tooth movements.

Microbiome analysis and predicted relative metabolomic turnover suggest bacterial heme and selenium metabolism are altered in the gastrointestinal system of zebrafish (Danio rerio) exposed to the organochlorine dieldrin.

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood.

Evaluation of Microbiome-Host Relationships in the Zebrafish Gastrointestinal System Reveals Adaptive Immunity Is a Target of Bis(2-ethylhexyl) Phthalate (DEHP) Exposure.

To improve physical characteristics of plastics such as flexibility and durability, producers enrich materials with phthalates such as di-2-(ethylhexyl) phthalate (DEHP). DEHP is a high production volume chemical associated with metabolic and immune disruption in animals and humans. To reveal mechanisms implicated in phthalate-related disruption in the gastrointestinal system, male and female zebrafish were fed DEHP (3 ppm) daily for two months. At the transcriptome level, DEHP significantly upregulated gene networks in the intestine associated with helper T cells' (Th1, Th2, and Th17) specific pathways. The activation of gene networks associated with adaptive immunity was linked to the suppression of networks for tight junction, gap junctional intercellular communication, and transmembrane transporters, all of which are precursors for impaired gut integrity and performance. On a class level, DEHP exposure increased Bacteroidia and Gammaproteobacteria and decreased Verrucomicrobiae in both the male and female gastrointestinal system. Further, in males there was a relative increase in Fusobacteriia and Betaproteobacteria and a relative decrease in Saccharibacteria. Predictive algorithms revealed that the functional shift in the microbiome community, and the metabolites they produce, act to modulate intestinal adaptive immunity. This finding suggests that the gut microbiota may contribute to the adverse effects of DEHP on the host by altering metabolites sensed by both intestinal and immune Th cells. Our results suggest that the microbiome-gut-immune axis can be modified by DEHP and emphasize the value of multiomics approaches to study microbiome-host interactions following chemical perturbations.

Consensus Clustering of temporal profiles for the identification of metabolic markers of pre-diabetes in childhood (EarlyBird 73).

In longitudinal clinical studies, methodologies available for the analysis of multivariate data with multivariate methods are relatively limited. Here, we present Consensus Clustering (CClust) a new computational method based on clustering of time profiles and posterior identification of correlation between clusters and predictors. Subjects are first clustered in groups according to a response variable temporal profile, using a robust consensus-based strategy. To discover which of the remaining variables are associated with the resulting groups, a non-parametric hypothesis test is performed between groups at every time point, and then the results are aggregated according to the Fisher method. Our approach is tested through its application to the EarlyBird cohort database, which contains temporal variations of clinical, metabolic, and anthropometric profiles in a population of 150 children followed-up annually from age 5 to age 16. Our results show that our consensus-based method is able to overcome the problem of the approach-dependent results produced by current clustering algorithms, producing groups defined according to Insulin Resistance (IR) and biological age (Tanner Score). Moreover, it provides meaningful biological results confirmed by hypothesis testing with most of the main clinical variables. These results position CClust as a valid alternative for the analysis of multivariate longitudinal data.

High-resolution analysis of the human retina miRNome reveals isomiR variations and novel microRNAs.

MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina.

Unravelling druggable signalling networks that control F508del-CFTR proteostasis.

Cystic fibrosis (CF) is caused by mutations in CF transmembrane conductance regulator (CFTR). The most frequent mutation (F508del-CFTR) results in altered proteostasis, that is, in the misfolding and intracellular degradation of the protein. The F508del-CFTR proteostasis machinery and its homeostatic regulation are well studied, while the question whether 'classical' signalling pathways and phosphorylation cascades might control proteostasis remains barely explored. Here, we have unravelled signalling cascades acting selectively on the F508del-CFTR folding-trafficking defects by analysing the mechanisms of action of F508del-CFTR proteostasis regulator drugs through an approach based on transcriptional profiling followed by deconvolution of their gene signatures. Targeting multiple components of these signalling pathways resulted in potent and specific correction of F508del-CFTR proteostasis and in synergy with pharmacochaperones. These results provide new insights into the physiology of cellular proteostasis and a rational basis for developing effective pharmacological correctors of the F508del-CFTR defect.

Mendelian disorders of PI metabolizing enzymes.

More than twenty different genetic diseases have been described that are caused by mutations in phosphoinositide metabolizing enzymes, mostly in phosphoinositide phosphatases. Although generally ubiquitously expressed, mutations in these enzymes, which are mainly loss-of-function, result in tissue-restricted clinical manifestations through mechanisms that are not completely understood. Here we analyze selected disorders of phosphoinositide metabolism grouped according to the principle tissue affected: the nervous system, muscle, kidney, the osteoskeletal system, the eye, and the immune system. We will highlight what has been learnt so far from the study of these disorders about not only the cellular and molecular pathways that are involved or are governed by phosphoinositides, but also the many gaps that remain to be filled to gain a full understanding of the pathophysiological mechanisms underlying the clinical manifestations of this steadily growing class of diseases, most of which still remain orphan in terms of treatment. This article is part of a Special Issue entitled Phosphoinositides.

Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi.

A fundamental property of cellular processes is to maintain homeostasis despite varying internal and external conditions. Within the membrane transport apparatus, variations in membrane fluxes from the endoplasmic reticulum (ER) to the Golgi complex are balanced by opposite fluxes from the Golgi to the ER to maintain homeostasis between the two organelles. Here we describe a molecular device that balances transport fluxes by integrating transduction cascades with the transport machinery. Specifically, ER-to-Golgi transport activates the KDEL receptor at the Golgi, which triggers a cascade that involves Gs and adenylyl cyclase and phosphodiesterase isoforms and then PKA activation and results in the phosphorylation of transport machinery proteins. This induces retrograde traffic to the ER and balances transport fluxes between the ER and Golgi. Moreover, the KDEL receptor activates CREB1 and other transcription factors that upregulate transport-related genes. Thus, a Golgi-based control system maintains transport homeostasis through both signaling and transcriptional networks.

Morbihan syndrome.

We report a case of severe Morbihan syndrome (chronic erythematous edema of the upper portion of the face) in a 60-year-old man. The syndrome was characterized clinically by erythematous edema involving the forehead, glabella, and both eyelids, because of which the patient was not able to open completely his eyes. Furthermore, erythema and telangiectasiae were visible on the nose and cheeks. Laboratory and instrumental examinations were within normal ranges or negative. Histopathological examination showed dermal edema, perivascular and periadnexal lympho-histiocytic infiltrate, and sebaceous gland hyperplasia. Oral isotretinoin was ineffective despite the relatively long duration of the therapy (26 weeks).

Follicular cutaneous larva migrans: a report of three cases and review of the literature.

BACKGROUND: Hookworm-related cutaneous larva migrans (CLM) is characterized clinically by erythematous and slightly raised tracks, located especially on the feet. These tracks may be single or multiple, linear or serpiginous, more or less ramified and intertwined. The length is variable (up to many cm); the width ranges from 1 mm to 4 mm. Tracks are often accompanied by severe pruritus. METHODS: Three adult Caucasian patients recently returned from trips to Malaysia and Thailand, presented with follicular CLM. The disease was characterized clinically by follicular, erythematous, small papules that were sometimes topped with vesicles or pustules, located on the buttocks. Pruritus was severe. RESULTS: Histopathological examinations revealed a perifollicular infiltrate predominantly consisting of lymphocytes and eosinophils. All patients were successfully treated with oral albendazole (400 mg/day for seven days). In the first patient, two courses were necessary. CONCLUSIONS: Dermatologists should be aware of the existence of this rare and atypical, although emerging, clinical presentation of hookworm-related CLM.

Chronic hookworm-related cutaneous larva migrans.

OBJECTIVES: The purpose of this study is to present the 'chronic' or 'persistent' form of hookworm-related cutaneous larva migrans. METHODS: From 1998 to 2011, 13 patients were seen in our department with clinically typical hookworm-related cutaneous larva migrans that had been present for more than 5 months and that, because of the absence of pruritus, had never been treated. RESULTS: The duration of hookworm-related cutaneous larva migrans ranged from 5 to 14 months (mean 7.8 months) in these 13 patients (10 males and three females, aged 23-55 years). The infestation was acquired in Brazil (three patients), Jamaica (three patients), Mexico (two patients), Tanzania (two patients), Thailand (two patients), and Martinique (one patient). The infestation was located on the feet in 10 patients; one of these patients also presented tracks on the back and another presented tracks on a knee. The chest (two patients) and thigh (two patients) were also involved. All patients presented with clinically typical hookworm-related cutaneous larva migrans: seven patients had one track and six patients had two tracks. Laboratory and instrumental examinations were within the normal range or negative. Histopathological examination revealed edema in the papillary and upper dermis, and a perivascular and perifollicular infiltrate in the upper dermis, consisting mainly of lymphocytes and eosinophils. No larvae were detected. CONCLUSIONS: This can be considered the 'chronic' or 'persistent' form of hookworm-related cutaneous larva migrans. Some pathogenetic hypotheses are suggested.

Isoconazole nitrate vs isoconazole nitrate and diflucortolone valerate in the treatment of tinea inguinalis: results of a multicenter retrospective study.

BACKGROUND AND OBJECTIVE: Many tinea inguinalis infections are characterized by pronounced inflammatory lesions and pruritus. Therefore, a therapy with a topical corticosteroid in addition to a topical antimycotic agent might be beneficial. In this multicenter, retrospective study, we compared the mycological and clinical efficacy and tolerability of isoconazole nitrate alone vs isoconazole nitrate and diflucortolone valerate in 58 adult patients with tinea inguinalis. PATIENTS AND METHODS: Treatment duration was three weeks. The efficacy of the treatment was based on the assessment of several signs and symptoms, which were collected on a 4-point scale. All patients were examined clinically before the beginning of the treatment, one week later, two weeks later, and at the end of the treatment. Mycological examinations were performed before the beginning of the treatment and at the end of the study. RESULTS: Treatment results with the combination of isoconazole nitrate and diflucortolone valerate were superior regarding erythema and pruritus. Both erythema and pruritus resolved in a larger percentage of patients and more quickly. Both regimens were well tolerated. Mycological cure rates were similar in both groups of patients. CONCLUSIONS: Combination therapy with isoconazole nitrate and diflucortolone valerate is an effective and well-tolerated regimen in adult patients with tinea inguinalis.

One-week therapy with oral albendazole in hookworm-related cutaneous larva migrans: a retrospective study on 78 patients.

We evaluated retrospectively the efficacy and tolerability of oral albendazole (400 mg/day for 1 week) in 78 patients with hookworm-related cutaneous larva migrans characterized by multiple and/or extensive lesions. The diagnosis was based on history and the clinical picture. Neither topical or systemic drugs nor physical treatments were used. All patients were followed-up for at least 3 months after the therapy. All patients were cured at the end of the therapy. The disappearance of pruritus was reported after 2-3 days and skin lesions after 5-7 days of therapy. One patient reported nausea and abdominal pain; another patient reported worsening of pruritus: in both cases it was not necessary to stop the therapy. No recurrences were observed during follow-up. One week of therapy with 400 mg/day oral albendazole is very effective (cure rate: 100%) in patients with cutaneous larva migrans characterized by multiple and/or extensive lesions. This therapeutical regimen is not accompanied by the appearance of new and/or more severe side effects.

Placental growth factor regulates cardiac inflammation through the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α-converting enzyme axis: crucial role for adaptive cardiac remodeling during cardiac pressure overload.

BACKGROUND: Heart failure is one of the leading causes of mortality and is primarily the final stage of several overload cardiomyopathies, preceded by an early adaptive hypertrophic response and characterized by coordinated cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors and cytokines have to be critically regulated during cardiac response to transverse aortic constriction. Interestingly, the dual properties of placental growth factor as an angiogenic factor and cytokine make it a candidate to participate in cardiac remodeling in response to hemodynamic overload. METHODS AND RESULTS: After transverse aortic constriction, placental growth factor knockout mice displayed a dysregulation of cardiac remodeling, negatively affecting muscle growth. Molecular insights underscored that this effect was ascribable mainly to a failure in the establishment of adequate inflammatory response owing to an impaired activity of tumor necrosis factor-α-converting enzyme. Interestingly, after transverse aortic constriction, placental growth factor knockout mice had strongly increased levels of tissue inhibitor of metalloproteinases-3, the main natural TACE inhibitor, thus indicating an unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α-converting enzyme axis. Strikingly, when we used an in vivo RNA interference approach to reduce tissue inhibitor of metalloproteinases-3 levels in placental growth factor knockout mice during transverse aortic constriction, we obtained a complete phenotype rescue of early dilated cardiomyopathy. CONCLUSIONS: Our results demonstrate that placental growth factor finely tunes a balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α-converting enzyme axis and the consequent TNF-α activation in response to transverse aortic constriction, thus allowing the establishment of an inflammatory response necessary for adaptive cardiac remodeling.

Tungiasis in a beach volleyball player: a case report.

Tungiasis is an infestation caused by penetration of the skin by the gravid female of the flea Tunga penetrans Linnaeus 1758 (Insecta, Siphonaptera: Tungidae). Tunga penetrans is currently found in Central and South America, sub-Saharan Africa, and Central Asia. Prevalence is very high in Brazil. We present a case of tungiasis in an Italian beach volleyball player who acquired the infestation in Brazil.

Age-related hearing loss in four Italian genetic isolates: an epidemiological study.

The objective of this study was to estimate the prevalence of hearing impairment in four genetically isolated Italian villages (Carlantino, Campora, Gioi-Cardile, and Stoccareddo), 1682 subjects were recruited from all the individuals participating in a multidisciplinary study. They underwent otoscopy and pure-tone audiometry and completed a questionnaire. The audiological data show that the percentage of impaired people increases with age and in particular becomes relevant aged over 40. For this reason we decided to compare the PTA values of individuals aged 40 or older. The PTA values of Stoccareddo and Carlantino are statistically different from PTAs of the other villages. Campora and Gioi-Cardile, both located within the Cilento National Park, have similar middle-low frequency PTA values while some differences are present at high frequencies. Using pedigrees it was possible to calculate the heritability of the trait. For Carlantino and Gioi-Cardile the percentage of the phenotype variation attributable to genetic variation is not significant, while for Campora the heritability value is 0.49 (p = 0.01) suggesting that genetic factors may have an important role.

Characterization of the functional properties of the neuroectoderm in mouse Cripto(-/-) embryos showing severe gastrulation defects.

During development of the mammalian embryo, there is a complex relation between formation of the mesoderm and the neuroectoderm. In mouse, for example, the role of the node and its mesendoderm derivatives in anterior neural specification is still debated. Mouse Cripto(-/-) embryos could potentially help settle this debate because they lack almost all embryonic endoderm and mesoderm, including the node and its derivatives. In the present paper, we show that Cripto(-/-) embryos can still form functional neural stem cells that are able to differentiate and maintain a neural phenotype both in vivo and in vitro. These data suggest that signals emanating from the mesoderm and endoderm might not be essential for the formation and differentiation of neural stem cells. However, we use grafting experiments to show that the Cripto(-/-) isthmus (the secondary organizer located at the midbrain-hindbrain boundary) loses its inductive ability. We further show that the Cripto(-/-)isthmus expresses lower amounts of the isthmic signalling molecule, Fgf8. Since nearby tissues remain competent to respond to exogenously added Fgf8, this reduction in Fgf8 levels in the Cripto(-/-) isthmus is the potential cause of the loss of patterning ability in graft experiments. Overall, we interpret our data to suggest that the mammalian node and primitive streak are essential for the development of the regional identities that control the specification and formation of the secondary organizers within the developing brain.

Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction.

The EGF-CFC gene cripto governs anterior-posterior (A-P) axis specification in the vertebrate embryo. Existing models suggest that Cripto facilitates binding of Nodal to an ActRII-activin-like kinase (ALK) 4 receptor complex. Cripto also has a crucial function in cellular transformation that is independent of Nodal and ALK4. However, how ALK4-independent Cripto pathways function in vivo has remained unclear. We have generated cripto mutants carrying the amino acid substitution F78A, which blocks the Nodal-ALK4-Smad2 signaling both in embryonic stem cells and cell-based assays. In cripto(F78A/F78A) mouse embryos, Nodal fails to expand its own expression domain and that of cripto, indicating that F78 is essential in vivo to stimulate Smad-dependent Nodal autoinduction. In sharp contrast to cripto-null mutants, cripto(F78A/F78A) embryos establish an A-P axis and initiate gastrulation movements. Our findings provide in vivo evidence that Cripto is required in the Nodal-Smad2 pathway to activate an autoinductive feedback loop, whereas it can promote A-P axis formation and initiate gastrulation movements independently of its stimulatory effect on the canonical Nodal-ALK4-Smad2 signaling pathway.

Identification and replication of a novel obesity locus on chromosome 1q24 in isolated populations of Cilento.

OBJECTIVE: Obesity is a complex trait with a variety of genetic susceptibility variants. Several loci linked to obesity and/or obesity-related traits have been identified, and relatively few regions have been replicated. Studying isolated populations can be a useful approach to identify rare variants that will not be detected with whole-genome association studies in large populations. RESEARCH DESIGN AND METHODS: Random individuals were sampled from Campora, an isolated village of the Cilento area in South Italy, phenotyped for BMI, and genotyped using a dense microsatellite marker map. An efficient pedigree-breaking strategy was applied to perform genome-wide linkage analyses of both BMI and obesity. Significance was assessed with ad hoc simulations for the two traits and with an original local false discovery rate approach to quantitative trait linkage analysis for BMI. A genealogy-corrected association test was performed for a single nucleotide polymorphism located in one of the linkage regions. A replication study was conducted in the neighboring village of Gioi. RESULTS: A new locus on chr1q24 significantly linked to BMI was identified in Campora. Linkage at the same locus is suggested with obesity. Three additional loci linked to BMI were also detected, including the locus including the INSIG2 gene region. No evidence of association between the rs7566605 variant and BMI or obesity was found. In Gioi, the linkage on chr1q24 was replicated with both BMI and obesity. CONCLUSIONS: Overall, our results confirm that successful linkage studies can be accomplished in these populations both to replicate known linkages and to identify novel quantitative trait linkages.