Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

Cardiomyopathy associated with dystrophinopathies [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-dCM) and cardiomyopathy of Duchenne/Becker (DMD/BMD) carriers] is an increasing recognized manifestation of these neuromuscular disorders and notably contributes to their morbidity and mortality. Dystrophinopathic cardiomyopathy (DCM) is the result of the dystrophin protein deficiency at the myocardium level, parallel to the deficiency occurring at the skeletal muscle level. It begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward pictures of overt cardiomyopathy (hypertrophic stage, arrhythmogenic stage and dilated cardiomyopathy). The final stage caused by the extensive loss of cardiomyocytes results in an irreversible cardiac failure, characterized by frequent episodes of acute congestive heart failure (CHF), despite a correct pharmacological treatment. The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of BMD, XL-dCM and cardiomyopathy of DMD/BMD carriers, while it is less frequently observed in patients with DMD. Heart transplantation (HT) is the only curative therapy for patients with dystrophinopathic end-stage heart failure who remain symptomatic despite an optimal medical therapy. However, no definitive figures exist in literature concerning the number of patients with DCM transplanted, and their outcome. This overview is to summarize the clinical outcomes so far published on the topic, to report the personal series of dystrophinopathic patients receiving heart transplantation and finally to provide evidence that heart transplantation is a safe and effective treatment for selected patients with end-stage DCM

Association between self-control and health risk behaviors: a cross-sectional study with 9th grade adolescents in São Paulo.

BACKGROUND: Self-control (SC) has been consistently found associated with diverse health risk behaviors (HRBs), but little research refers to low- and middle-income countries. Furthermore, there is evidence that some HRBs tend to aggregate, however studies with the specific purpose of addressing the relation between SC and multiple health risk behaviors (MHRBs) are rare. The objective of this study is to analyze these associations and provide evidence to help filling these gaps. METHODS: A sample of 2106 9th grade students from the city of São Paulo responded a self-administered questionnaire in 2017. We tested the association of SC measured as an ordinal variable with four levels (higher, high, medium and low) with six HRBs (binge drinking, marijuana use, smoking, high consumption of ultra-processed food, sedentary behavior and bullying perpetration), in both separated and aggregated forms (MHRBs), controlling for potential confounders. Binary logistic regression was used to test the association between exposure (SC) and single outcomes. In order to analyze the association of SC with MHRBs, multinomial logistic regression was employed. RESULTS: SC was associated with five of six HRBs investigated and with MHRBs. The effect size of the association of SC and MHRBs increased in a steep pattern with accumulation of more HRBs. CONCLUSION: Low self-control is associated with most HRBs investigated and the magnitude of the association increases when more than two or three HRBs are accumulated. There seems to be a group of adolescents in a position of pronounced vulnerability for MHRBs. This should be considered when designing public policy and prevention programs. In contexts of limited or scarce resources and public funds, interventions focusing the most vulnerable groups, instead of universal interventions, should be considered

The Genetic resistence to Coccidia in Appenninica sheep

The study was conducted on a single herd of Appenninica sheep breed situated in Tuscany (Italy) from April to November 2004 on 108 sheep with the aim to identify the most resistant subjects to Coccidia. Moreover, the presence of gastro-intestinal Strongylids, Dicrocoelium sp. Moniezia spp.Strongyloides sp. and Trichuris sp. was also evaluated. Sheep selection may be based on OPG in adults animals, as it appears to be an indicator of sheep resistance to Coccidia. Before incorporating the parameter into breeding programmes, however, it is necessary to better appraise the degree of infestation of the other parasites as it may be difficult to select simultaneously for resistance to Coccidia and Strongylids unless the genetic correlation between these two traits is calculated and a selection index approach is used

Evaluation of salivary matrix metalloproteinase (MMP-8) in periodontal patients undergoing non-surgical periodontal therapy and mouthwash based on ozonated olive oil: a randomized clinical trial

Background: Extracellular matrix metalloproteinases (MMPs) play a pivotal role in the damage to the periodontal tissue in patients with periodontitis. Scaling and root planning (SRP) attempt to control the plaque amount and consequentially reduce the bacterial load. Non-surgical periodontal treatment could be integrated with drug therapy and physiotherapy procedures such as ozone therapy. The aim of this study was to evaluate in a cohort of patients with a diagnosis of periodontitis: (1) the efficacy of non-surgical periodontal therapy assisted by the use of ozonated olive oil-based mouthwash on salivary metalloproteinase (MMP-8) and (2) the reduction of periodontal indices. Methods: Ninety-six subjects with a diagnosis of periodontitis were enrolled in this study and randomly assigned to the study group (SRP + mouthwash) or control group (SRP). The study duration was 3 months. Data on MMP-8, plaque index (PI), bleeding on probing (BoP) and probing pocket depth (PPD) were recorded at T0, T1 (14 days), T2 (1 month) and T3 (6 months). Group differences were assessed using Student’s t-test for independent samples. Results: A significant improvement in PI, BoP, PPD and salivary MMP-8 levels was observed in both groups. An analysis of differences in relative changes of indices revealed the efficacy of ozonated olive oil in decreasing MMP-8 level. Simultaneously, it slowed the decrease of BoP index. Conclusions: Scaling and root plaining with the aid of ozonated olive oil mouthwash were found to be more effective on salivary MMP-8 reduction than scaling and root plaining alone

Synergistic Proapoptotic Activity of Recombinant Trail Plus the AKT Inhibitor Perifosine in Acute Myelogenous Leukemia Cells

To potentiate the response of acute myelogenous leukemia (AML) cells to TNF-Related Apoptosis- Inducing Ligand (TRAIL) cytotoxicity, we have examined the efficacy of a combination with perifosine, a novel phosphatidylinositol 3-kinase (PI3K)/Akt signaling inhibitor. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease the cellular FLICE-Inhibitory Protein (cFLIP) in human lung cancer cell lines. Perifosine and TRAIL both induced cell death by apoptosis in the THP-1 AML cell line, which is characterized by constitutive PI3K/Akt activation, but lacks functional p53. Perifosine, at concentrations below IC50, dephosphorylated Akt and increased TRAIL-R2 levels, as demonstrated by western blot, RT-PCR, and flow cytometric analysis. Perifosine also decreased the long isoform of cFLIP (cFLIP-L) and the X-linked Inhibitor of Apoptosis Protein (XIAP) expression. Perifosine and TRAIL synergized to activate caspase-8 and induce apoptosis, which was blocked by a caspase- 8 selective inhibitor. Upregulation of TRAIL-R2 expression was dependent on a protein kinase Cα/ c-Jun-NH2-kinase 2/c-Jun signaling pathway activated by perifosine through reactive oxygen species production. Perifosine synergized with TRAIL also in primary AML cells displaying constitutive activation of the Akt pathway, by inducing apoptosis, Akt dephosphorylation, TRAIL-R2 upregulation, cFLIP-L and XIAP downregulation, and c-Jun phosphorylation. The combined treatment negatively affected the clonogenic activity of CD34+ cells from AML patients. In contrast, CD34+ cells from healthy donors were resistant to perifosine and TRAIL treatment. Our findings suggest that the combination perifosine and TRAIL might offer a novel therapeutic strategy for AML. Originally published Cancer Research, Vol. 68, No. 22, Nov 200

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful

Dysregulation of oncogenic factors by GFI1B p32: investigation of a novel GFI1B germline mutation

GFI1B is a transcription factor essential for the regulation of erythropoiesis and megakaryopoiesis, and pathogenic variants have been associated with thrombocytopenia and bleeding. Analysing thrombocytopenic families by whole exome sequencing, we identified a novel GFI1B variant (c.648+5G>A), which causes exon 9 skipping and overexpression of a shorter p32 isoform. We report the clinical data of our patients and critically review the phenotype observed in individuals with different GFI1B variants leading to the same effect on the p32 expression. Since p32 is increased in acute and chronic leukemia cells, we tested the expression level of genes playing a role in various type of cancers, including hematological tumors and found that they are significantly dysregulated, suggesting a potential role for GFI1B in carcinogenesis regulation. Increasing the number of individuals with GFI1B variants will allow us to better characterize this rare disease and determine whether it is associated with an increased risk of developing malignancies

How should ecohazard of micropollutants in wastewater be gauged? Using bioassays to profile alternative tertiary treatments

The research on emerging pollutants in wastewater has become a worldwide issue of increasing environmental concern, especially considering the growing interest in wastewater reuse. However, the latter implies additional post-treatment after the conventional activated sludge processes, in order to produce a safer effluent. Our work aimed at determining the efficiency of reducing the toxicity associated with organic micropollutants (OMPs) in secondary wastewater effluents, using 3 different post-treatment technologies (granular activated carbon (GAC), sand biofiltration and UV irradiation): in particular, target chemical analysis of the OMPs most commonly founded in wastewater was coupled with effect-based assays (estrogenicity and mutagenicity). While chemical analysis assessed satisfactory performances for all 3 technologies in the abatement of selected OMPs, biological assays evidenced another perspective: both GAC and sand biofilters were significantly able to make the estrogenic load plummet; however, the UV system was ineffective in estrogenicity abatement, and its effluent exhibited also a slight mutagenicity, likely due to photo-transformation by-products. These results indicate that a synergistic combination of chemical analysis and biological assays can drive to a proper gauging of post-treatment technologies, taking into account not only the removal of OMPs, but also their overall toxicityThis work was conceived within a Short Term Scientific Mission (STSM) of the Water2020 Cost Action ES1202: Conceiving Wastewater Treatment in 2020 | Energetic, environmental and economic challenges. Authors from Universidade de Santiago de Compostela belong to the Galician Competitive Research Group GRC 2013-032 and to the CRETUS Strategic Partnership (AGRUP2015/02). All these programmes are co-funded by FEDER (UE)S