Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence

Background Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. Methods PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. Results Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. Conclusions The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs

Characterization of Epstein Barr Virus Latency Pattern in Argentine Breast Carcinoma

INTRODUCTION: Epstein-Barr virus (EBV)-associated tumors show different expression patterns of latency genes. Since in breast carcinoma this pattern is not yet fully described, our aim was to characterize EBV latency pattern in our EBV positive breast carcinoma series. METHODS: The study was conducted on 71 biopsies of breast carcinoma and in 48 non-neoplastic breast controls. EBNA1, LMP2A and LMP1 expression was assessed by immunohistochemistry with monoclonal antibodies, while viral genomic DNA and EBERs RNA transcripts expression was performed by in situ hybridization. EBV presence was confirmed by PCR. RESULTS: EBV genomic DNA and EBNA1 expression were detected in 31% (22/71) of patients specifically restricted to tumor epithelial cells in breast carcinoma while all breast control samples were negative for both viral DNA and EBNA1 protein. LMP2A was detected in 73% of EBNA1 positive cases, none of which expressed either LMP1 protein or EBERs transcripts. CONCLUSIONS: These findings suggest that EBV expression pattern in the studied biopsies could be different from those previously observed in breast carcinoma cell lines and lead us to suggest a new, EBNA1, LMP2A positive and LMP1 and EBERs negative latency profile in breast carcinoma in our population

Epstein Barr virus in relation to apoptosis markers and patients' outcome in pediatric B-cell Non-Hodgkin lymphoma

In this study, we investigated Epstein Barr virus (EBV) presence, associated to proliferation and apoptosis proteins in pediatric B-cell Non-Hodgkin lymphoma (B-NHL). EBERs, Ki67, active caspase 3, Bax and Bcl2 were analyzed on B-NHL tissue from 40 patients. Forty percent showed EBV expression, significantly higher among patients ≤10. years (P= 0.027), and associated with immunosuppression (P= 0.020), but not associated apotosis markers. However, EBV was associated with a worse event-free survival (P= 0.016), particularly under immunosuppression. Even though EBV did not seem to alter apoptotic pathways, it exhibited survival disadvantage and could be an important cofactor in B-cell lymphomagenesis in younger children.Fil: Chabay, Paola Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lara, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Lorenzetti, Mario Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cambra, P.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Acosta Haab, G.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Aversa, L.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Molecular alterations in the integrated diagnosis of pediatric glial and glioneuronal tumors: A single center experience

Objectives: Tumors of the central nervous system (CNS) are the most common pediatric solid tumors, where low grade (LGG) and high grade gliomas (HGG) represent up to 55% of CNS tumors. Current molecular classification of these tumors results in a more accurate diagnosis and risk stratification, which ultimately enables individualized treatment strategies. Identifying known alterations is a suitable approach, particularly in developing countries, where NGS approaches are not easily accessible. We sought to assess molecular alterations in BRAF and histone 3 genes. Study design: FISH, IHC and Sanger sequencing were performed in a series of 102 pediatric glial and glioneuronal tumors. We also correlated these results with clinical and histological findings to evaluate their usefulness as diagnostic and/or prognostic tools. Results: We found that the KIAA1549-BRAF gene fusion was a relevant diagnostic tool for pilocytic astrocytoma, but not related to progression free survival (PFS) and overall survival (OS). BRAFV600E mutation was associated with a decreased OS in LGG, and with decreased PFS and OS among pilocytic astrocytomas. All HGG of the midline were H3K27M mutants, while H3G34R mutant cases were located in brain hemispheres. HGG harboring the H3K27M variant were associated with a decreased PFS and OS. Conclusions: Assessing druggable molecular markers with prognostic value is particularly important in those cases where complete resection or further radiation therapy is not possible. These potential diagnostic/prognostic markers may be suitable as further screening tests to reduce the requirement on NGS, which is not available in all laboratories. Furthermore, these results broaden data on BRAF and Histone 3 alterations in children from geographic regions, other than USA and Europe.Fil: Colli, Sandra Lorena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Cardoso, Nazarena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Massone, Carla Antonella. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Cores, María. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: García Lombardi, Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Lorenzetti, Mario Alejandro. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentin

Comprehensive evolutionary analysis of complete Epstein Barr virus genomes from Argentina and other geographies

The sequence variability of the Epstein–Barr virus has been extensively studied throughout previous years in isolates from various geographic regions and consequent variations at both genetic and genomic levels have been described. However, isolates from South America were underrepre-sented in these studies. Here, we sequenced 15 complete EBV genomes that we analyzed together with publicly available raw NGS data for 199 EBV isolates from other parts of the globe by means of a custom-built bioinformatic pipeline. The phylogenetic relations of the genomes, the geographic structure and variability of the data set, and the evolution rates for the whole genome and each gene were assessed. The present work contributes to overcoming the scarcity of complete EBV genomes from South America and is the most comprehensive geography-related variability study, which involved determining the actual contribution of each EBV gene to the geographic segregation of the entire genome. Moreover, to the best of our knowledge, we established for the first time the evolution rate for the entire EBV genome based on a host–virus codivergence-independent assumption and assessed their evolution rates on a gene-by-gene basis, which were related to the encoded protein function. Considering the evolution of dsDNA viruses with a codivergence-independent approach may lay the basis for future research on EBV evolution. The exhaustive bioinformatic analysis performed on this new dataset allowed us to draw a novel set of conclusions regarding the genome evolution of EBV.Fil: Blazquez, Ana Catalina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Berenstein, Ariel José. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Torres, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Lorenzetti, Mario Alejandro. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentin

Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence)

Background Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. Main body The aim of this work is to provide recommendations for the diagnosis and management of people affected by Poland syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years affected subjects. The literature search was performed in the second half of 2019. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. Conclusion Being Poland syndrome a rare syndrome most recommendations here presented are good clinical practice based on the consensus of the participant experts

Recombination rates along the entire Epstein Barr virus genome display a highly heterogeneous landscape

Epstein Barr virus (EBV) has a large DNA genome assumed to be stable, but also subject to mutational processes such as nucleotide substitution and recombination, the latter explored to a lesser extent. Moreover, differences in the extent of recombination events across herpes sub-families were recently reported. Given the relevance of recombination in viral evolution and its possible impact in pathogenesis, we aimed to fully characterize and quantify its extension in all available EBV complete genome by assessing global and local recombination rate values (⍴/bp).Our results provide the first EBV recombination map based on recombination rates assessment, both at a global and gene by gene level, where the mean value for the entire genome was 0.035 (HPDI 0.020-0.062) ⍴/bp. We quantified how this evolutionary process changes along the EBV genome, and proved it to be non-homogeneous, since regulatory regions depicted the lowest recombination rate values while repetitive regions the highest signal. Moreover, GC content rich regions seem not to be linked to high recombination rates as previously reported.At an intragenic level, four genes (EBNA3C, EBNA3B, BRRF2 and BBLF2-BBLF3) presented a recombination rate above genome average. We specifically quantified the signal strength among different recombination-initiators previously described features and concluded that those which elicited the greatest amount of changes in ⍴/bp, TGGAG and CCCAG, were two well characterized recombination inducing motifs in eukaryotic cells. Strikingly, although TGGAG was not the most frequently detected DNA motif across the EBV genome (697 hits), it still induced a significantly greater proportion of initiation events (0.025 events/hits) than other more represented motifs, p-value = 0.04; one tailed proportion test.Present results support the idea that diversity and evolution of herpesviruses are impacted by mechanisms, such as recombination, which extends beyond the usual consideration of point mutations.Fil: Berenstein, Ariel José. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Lorenzetti, Mario Alejandro. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentin

A novel recombinant variant of latent membrane protein 1 from Epstein Barr virus in Argentina denotes phylogeographical association.

AIM:To study LMP1 variants distribution among children with EBV+ malignant and benign conditions as well as in healthy carriers. METHODS:Oral secretions and blood cells from 31 children with IM, and biopsies from 14 EBV+ reactive lymphoid hyperplasia and 33 EBV+ lymphomas were included. LMP1 was amplified by nested PCR and sequenced. Phylogenetic reconstructions were made under Maximun Likelihood, Bayesian and coalescent algorithms. RESULTS:Six clades were defined (China1, China2, Med-, Alaskan, B95.8 and Argentine). Argentine variants, the most prevalent (46%), harbored 3 distinctive mutations and were a recombination between Raji and China1. Despite no pathology or compartment associations were observed for LMP1, the Argentine clade showed a phylogeographic association with our region. LMP1 estimated evolution rate was 8.591x10-5s/s/y and the estimated tMRCA for Raji and Argentine was 136ybp. CONCLUSIONS:An LMP1 Argentine clade was defined. LMP1 evolutionary rate was higher than expected for herpesviruses. The tMRCA for Raji and the Argentine agrees with African immigration and could explain the recombinant nature of the Argentine variant

Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

The ubiquitous Epstein-Barr virus (EBV) is related to the development of several lymphoid and epithelial malignancies and is also the aetiological agent for infectious mononucleosis (IM). BZLF1, an immediate early gene, plays a key role in modulating the switch from latency to lytic replication, hence enabling viral propagation. Polymorphic variations in the coded protein have been studied in other geographical regions in a search for viral factors that are inherent to malignancies and differ from those present in benign infections. In the present study, in samples of paediatric patients with benign IM and paediatric patients with malignant lymphomas, we detected previously described sequence variations as well as distinctive sequence polymorphisms from our region. By means of phylogenetic reconstruction, we characterized new phylogenetically distinct variants. Moreover, we described an association between specific variants and the studied pathologies in our region, particularly variant BZLF1-A2 with lymphomas and BZLF1-C with IM. Additionally, length polymorphisms within intron 1 were also assessed and compared between pathologies resulting in an association between 29-bp repeated units and lymphomas. In conclusion, this is the first report to characterize BZLF1 gene polymorphisms in paediatric patients from our geographical region and to suggest the association of these polymorphisms with malignant lymphomas.Fil: Lorenzetti, Mario Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gantuz, Magdalena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Matteo Elena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chabay, Paola Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin