Open-source,vendor-independent,automated multi-beat tissue Doppler echocardiography analysis

Current guidelines for measuring cardiac function by tissue Doppler recommend using multiple beats, but this has a time cost for human operators. We present an open-source, vendor-independent, drag-and-drop software capable of automating the measurement process. A database of ~8000 tissue Doppler beats (48 patients) from the septal and lateral annuli were analyzed by three expert echocardiographers. We developed an intensity- and gradient-based automated algorithm to measure tissue Doppler velocities. We tested its performance against manual measurements from the expert human operators. Our algorithm showed strong agreement with expert human operators. Performance was indistinguishable from a human operator: for algorithm, mean difference and SDD from the mean of human operators’ estimates 0.48?±?1.12 cm/s (R²?=?0.82); for the humans individually this was 0.43?±?1.11 cm/s (R²?=?0.84), ?0.88?±?1.12 cm/s (R²?=?0.84) and 0.41?±?1.30 cm/s (R²?=?0.78). Agreement between operators and the automated algorithm was preserved when measuring at either the edge or middle of the trace. The algorithm was 10-fold quicker than manual measurements (p?<?0.001). This open-source, vendor-independent, drag-and-drop software can make peak velocity measurements from pulsed wave tissue Doppler traces as accurately as human experts. This automation permits rapid, bias-resistant multi-beat analysis from spectral tissue Doppler images.     

Psychological and Emotional Impact of COVID-19 Pandemic on People Living with Chronic Disease: HIV and Cancer

AIDS and Behavior - People living with chronic disease (PLWCD) are the frailest category, both for the risk of severe COVID-19 illness and for the impact on the care continuum. Aim of this study...     

The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update

So far, innate immune mechanisms have been recognized as the main responsible for the evolution of both alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). However, increasing evidence points toward the possible role of adaptive immune responses, as an additional factor in promoting hepatic inflammation in steatohepatitis. In this article, we discuss recent data involving circulating antibodies and lymphocyte-mediated responses in sustaining the progression of ASH and NASH to fibrosis, as well as the possible mechanisms implicated in favoring the onset of adaptive immunity in the setting of steatohepatitis.     

Drugs and psychoactive substances in the Tiber River

Wastewater analysis is a direct and objective method used to measure human consumption of illicit drugs. In the last few years these have become a new class of environmental contaminants. The aim of our study was the identification of drugs in Tiber River waters. We collected 20 water samples from May to June 2012, at six points of the river: at the source, near Perugia, near Rome and at the mouth. Samples were analysed using gas chromatography with a mass detector. Basic analytes were extracted using the method of Varian Certify. For acidic analytes we proceed to direct extraction using organic solvents. The most detected drug was ecstasy. We also identified traces of methadone, morphine, heroine, methylamphetamine and tetrahydrocannabinol (THC). The highest concentration of cocaine was found near Perugia with a peak in the weekend (4744 ng/ml). Psychoactive substances had constant concentrations in the week. Ecstasy (MDMA) was the most detected drug. The most interesting finding was the increased concentration of cocaine and heroin in waters near Perugia showing the alarming phenomenon of weekend use of these substances.     

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Background:  Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D₁ receptors in these effects.
Methods:  Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D₁ receptor antagonist, SCH 39166 (SCH) (50 μg/kg), was administered 10 minutes before ethanol (1 g/kg).
Results:  Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.
Conclusions:  The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D₁ receptor-mediated mechanism. Overall, these results suggest that the D₁ receptors/ERK pathway may play a critical role in the motivational properties of ethanol.     

The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.     

Genomic heterogeneity of hepatitis B virus (HBV) and outcome of perinatal HBV infection

BACKGROUND/AIMS: Data regarding hepatitis B virus (HBV) genomic heterogeneity in perinatal infection are incomplete, although HBV variants might be involved in neonatal fulminant hepatitis (ALF). We investigated HBV variability in infected babies showing different clinical courses. METHODS: We analyzed HBV genomes isolated from nine vertically infected babies and the mothers of four of them. Two infants born to HBe-antigen (HBeAg)-positive women developed a chronic infection; seven babies (six born to anti-HBe mothers) developed acute hepatitis that had a fulminant course in four cases and a benign course in three. Two babies developing ALF received anti-HBV immunoprophylaxis at birth. RESULTS: Viruses carrying no significant mutation infected infants born to HBeAg-positive women. HBeAg-defective viruses were detected both in children with benign and fulminant hepatitis and their mothers. A double nucleotide mutation at positions 1762 and 1764 of the HBV core-promoter was found in two of the four infants with ALF, although it was not detected in isolates from the mother of one of them. No significant S gene mutation was found in HBV from any of the babies. CONCLUSIONS: This study indicates that HBV genomic heterogeneity is not primarily involved either in the evolution of the infection or the failure of neonatal HBV immunoprophylaxis.     

Fludarabine,ara-C,novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients

BACKGROUND AND OBJECTIVES: The objective of improving the quality of responses of chronic lymphocytic leukemia (CLL) patients has led to the design of protocols that combine fludarabine (FDR) with synergistic drugs. We evaluated the efficacy and toxicity of a schedule that includes fludarabine, ara-C, novantrone and dexamethasone (FAND) for the management of previously treated CLL patients under 60 years old. DESIGN AND METHODS: Thirty-one patients underwent FAND treatment. Twenty-three patients had active disease (relapsed patients: 9; unresponsive to prior therapy: 14). Eight patients had a partial response (PR) to prior therapy and were treated with the aim of further reducing residual disease. The FAND schedule included fludarabine (25 mg/m(2) i.v. days 1-3), ara-C (1 g/m(2) i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m(2) i.v. day 1) and dexamethasone (20 mg i.v. days 1-3). Infection prophylaxis consisted of fluconazole, acyclovir, trimethoprim/sulfamethoxasole and granulocyte colony-stimulating factor (G-CSF) in the presence of severe neutropenia. RESULTS: A response was observed in 7/14 refractory patients (complete response-CR: 29%), in all 9 relapsed patients (CR: 78%) and in 7/8 patients (CR: 87.5%) treated in PR. Taken together, 18 CRs were obtained and in 14 (78%) this was associated with a flow cytometric remission (CD5+/CD20(weak+) PB lymphocytes: <10%). Severe granulocytopenia occurred after 86 of the 124 administered courses (69%), but only after 10/86 courses (12%) were major infections recorded. In 10/15 mobilized patients (cyclophosphamide + G-CSF: 6 patients; FAND + G-CSF: 9 patients) after FAND > or = 2 x 10(6)/kg CD34+ cells were collected. Nine patients were autografted in CR and showed a longer response duration than the 9 patients in CR who did not receive further therapy after FAND (53 vs 30% at 41 months; p = 0.05). INTERPRETATION AND CONCLUSIONS: FAND associated with extensive infection prophylaxis and G-CSF support is a highly cytoreductive and well-tolerated treatment for CLL patients and in most cases does not hamper subsequent stem cell mobilization.