Whole exome sequencing in an Italian family with isolated maxillary canine agenesis and canine eruption anomalies

Objective: The aim of this study was the clinical and molecular characterization of a family segregating a trait consisting of a phenotype specifically involving the maxillary canines, including agenesis, impaction and ectopic eruption, characterized by incomplete penetrance and variable expressivity. Design: Clinical standardized assessment of 14 family members and a whole-exome sequencing (WES) of three affected subjects were performed. WES data analyses (sequence alignment, variant calling, annotation and prioritization) were carried out using an in-house implemented pipeline. Variant filtering retained coding and splice-site high quality private and rare variants. Variant prioritization was performed taking into account both the disruptive impact and the biological relevance of individual variants and genes. Sanger sequencing was performed to validate the variants of interest and to carry out segregation analysis. Results: Prioritization of variants “by function” allowed the identification of multiple variants contributing to the trait, including two concomitant heterozygous variants in EDARADD (c.308C>T, p.Ser103Phe) and COL5A1 (c.1588G>A, p.Gly530Ser), specifically associated with a more severe phenotype (i.e. canine agenesis). Differently, heterozygous variants in genes encoding proteins with a role in the WNT pathway were shared by subjects showing a phenotype of impacted/ectopic erupted canines. Conclusions: This study characterized the genetic contribution underlying a complex trait consisting of isolated canine anomalies in a medium-sized family, highlighting the role of WNT and EDA cell signaling pathways in tooth development

Nonclassical roles for IFN-γand IL-10 in a murine model of immunoedition

Aims: to characterize, by means of univariate and multivariate approaches, the Th1 and Th2 responses during the different phases of tumor immunoediting. Materials & Methods: we used a multivariate principal component analysis applied to analyze the joint behavior of serum concentrations of IFN-γ, IL-2, IL-10 and IL-4, during the different phases of tumor immunoediting, in CBi/L mice challenged with M-406 mammary adenocarcinoma. Results & Conclusions: Animals in equilibrium phase showed the widest variations in values of the four cytokines. In this experimental model the role of IFN-γ would be related to tumor growth and progression, while IL-10 would participate in the antitumor immune response. Lay abstract: Breast cancer is a complex, multifactor disease that affects about 10% of women in industrialized countries. The immune system has the ability to monitor the appearance of tumors, but the tumors have the ability to escape such rejection. For this reason, in order to design different therapeutic strategies, it is important to know the different mechanisms that take place when a tumor grows or when it is rejected. Here we sought to elucidate some of these mechanismsFil: del Giúdice, Antonela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; ArgentinaFil: Mainetti, Leandro Ernesto. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Scharovsky, Olga Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigaciones de la Universidad de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Di Masso, Ricardo Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigaciones de la Universidad de Rosario; ArgentinaFil: Rico, Maria Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71–82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan1 Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets

Exploración de patrones de prescripción de ansiolíticos, hipnóticos y antidepresivos en hospitales y farmacias comunitarias de distintas regiones de la Argentina

Los estudios de utilización de medicamentos son herramientas útiles a fin de poder identificar consecuencias directas del uso (no-uso y abuso) de medicamentos sobre distintos aspectos de la vida de las personas insertas en la sociedad. La clasificación de los medicamentos en función de la categoría Anatómico Terapéutico Químico (Anatomical Therapeutic Chemical-ATC) y el uso de Dosis Diaria Definida (DDD), como unidad de medida para cuantificar el consumo de medicamentos permite realizar estimaciones del número de personas expuestas a un fármaco concreto. Los psicofármacos son sustancias natural y sintética que modifican funciones psíquicas sobre el sistema nervioso central (SNC); este tipo de productos en especialidades medicinales son utilizados para enfermedades psíquicas y neurológicas. El uso indiscriminado de estos medicamentos no está exento de reacciones adversas, y riesgos para la salud humana, lo cual genera discrepancia entre las recomendaciones académico-científicas sobre su prescripción y el uso en la práctica médica diaria. El objetivo de este trabajo es estudiar patrones de prescripción de ansiolíticos, hipnóticos y antidepresivos en una muestra de hospitales y farmacias comunitarias de la Argentina y su impacto económico.Fil: Bertoldo, Pamela. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; Argentin

Exploración de patrones de prescripción de ansiolíticos, hipnóticos y antidepresivos en hospitales y farmacias comunitarias de distintas regiones de la Argentina

Los estudios de utilización de medicamentos son herramientas útiles a fin de poder identificar consecuencias directas del uso (no-uso y abuso) de medicamentos sobre distintos aspectos de la vida de las personas insertas en la sociedad. La clasificación de los medicamentos en función de la categoría Anatómico Terapéutico Químico (Anatomical Therapeutic Chemical-ATC) y el uso de Dosis Diaria Definida (DDD), como unidad de medida para cuantificar el consumo de medicamentos permite realizar estimaciones del número de personas expuestas a un fármaco concreto. Los psicofármacos son sustancias natural y sintética que modifican funciones psíquicas sobre el sistema nervioso central (SNC); este tipo de productos en especialidades medicinales son utilizados para enfermedades psíquicas y neurológicas. El uso indiscriminado de estos medicamentos no está exento de reacciones adversas, y riesgos para la salud humana, lo cual genera discrepancia entre las recomendaciones académico-científicas sobre su prescripción y el uso en la práctica médica diaria. El objetivo de este trabajo es estudiar patrones de prescripción de ansiolíticos, hipnóticos y antidepresivos en una muestra de hospitales y farmacias comunitarias de la Argentina y su impacto económico.Fil: Bertoldo, Pamela. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; Argentin

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

Uncertainties and controversies in axillary management of patients with breast cancer

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register

Italian Guidelines in diagnosis and treatment of alopecia areata

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs). Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance. Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients. Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns