Lateral patellar luxation in nine small breed dogs

The objective of this paper was to describe the clinical features, the management and the outcome of nine small breed dogs affected with lateral patella luxation referred during the period between January 2010 and December 2014. Patellar luxations were classified according to: breed, age, sex, weight, and grade of patellar luxation, as well as if unilateral or bilateral, and concurrent cranial cruciate ligament lesion. In affected dogs, surgical correction consisted in the combination of tibial tuberosity transposition and soft tissue procedure. Adjunctive condroplasty or trochleoplasty was performed as needing. The outcome was found positive after surgical management with low complication rate and complications have been easily managed with high success rate

Comparing the effects of combined numerical and visuospatial psychoeducational trainings conducted by curricular teachers and external trainers. Preliminary evidence across kindergarteners

The aim of this study was to verify the efficacy of two pencil-and-paper trainings empowering numerical and visuo-spatial abilities in Italian five-year-old kindergarteners. Specifically, the trainings were respectively carried out by the curricular teacher or by an external trainer. The former received a specific training in order to use the psychoeducational programmes with her pupils, whereas the latter received a specific education about the role of numerical and visuo-spatial abilities for school achievement and she was also trained to use psychoeducational trainings in kindergarten schools. At pre-test and post-test nonverbal functions and numeracy knowledge were assessed through a battery of standardized tests. The results show that both the numerical psychoeducational programme and the visuo-spatial one are useful tools to enhance mathematical achievements in kindergarteners. However, when the trainings were proposed by the external trainer, the efficacy of the psychoeducational programmes was more significant. These outcomes seem to be related both to the expertise and the novelty effect of the external trainer on the classroom

Local Guidance of Emerging Vessel Sprouts Requires Soluble Flt-1

Blood vessel networks form via sprouting of endothelial cells from parent vessels. Extrinsic cues guide sprouts once they leave the initiation site, but these cues are likely insufficient to regulate initial outward movement, and many embryonic vessel networks form in the absence of a strong extrinsic gradient. We hypothesized that nascent sprouts are guided by spatial cues produced along their own vessels, and that soluble Flt-1 (sFlt-1) participates in this guidance. Analysis of developing vessels with perturbed flt-1 function revealed mis-guided emerging sprouts, and transgenic sFlt-1 rescued sprout guidance parameters. sFlt-1 activity in endothelial cells immediately adjacent to the emerging sprout significantly improved local sprout guidance. Thus we propose that a vessel-intrinsic system initially guides emerging sprouts away from the parent vessel, utilizing spatially regulated expression of sFlt-1 in conjunction with exogenous VEGF. Local sprout guidance defects are predicted to contribute to vessel dysmorphogenesis during perturbed development and disease

The unprecedented optical outburst of the quasar 3C 454.3. The WEBT campaign of 2004-2005

The radio quasar 3C 454.3 underwent an exceptional optical outburst lasting more than 1 year and culminating in spring 2005. The maximum brightness detected was R = 12.0, which represents the most luminous quasar state thus far observed (M_B ~ -31.4). In order to follow the emission behaviour of the source in detail, a large multiwavelength campaign was organized by the Whole Earth Blazar Telescope (WEBT). Continuous optical, near-IR and radio monitoring was performed in several bands. ToO pointings by the Chandra and INTEGRAL satellites provided additional information at high energies in May 2005. The historical radio and optical light curves show different behaviours. Until about 2001.0 only moderate variability was present in the optical regime, while prominent and long-lasting radio outbursts were visible at the various radio frequencies, with higher-frequency variations preceding the lower-frequency ones. After that date, the optical activity increased and the radio flux is less variable. This suggests that the optical and radio emissions come from two separate and misaligned jet regions, with the inner optical one acquiring a smaller viewing angle during the 2004-2005 outburst. Moreover, the colour-index behaviour (generally redder-when-brighter) during the outburst suggests the presence of a luminous accretion disc. A huge mm outburst followed the optical one, peaking in June-July 2005. The high-frequency (37-43 GHz) radio flux started to increase in early 2005 and reached a maximum at the end of our observing period (end of September 2005). VLBA observations at 43 GHz during the summer confirm theComment: 7 pages, 4 figures, to be published in A&

VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy

Peer reviewe

Predicting mental health improvement and deterioration in a large community sample of 11- to 13-year-olds

Multivariate analysis of psychological dat

Platelet activation is associated with myocardial infarction in patients with pneumonia

BACKGROUND: Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.OBJECTIVES: The aim of this study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.METHODS: A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.RESULTS: Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB2 (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs (p = 0.005).CONCLUSIONS: MI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863)

Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development

Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial

BACKGROUND: Statins have beneficial effects on intrahepatic circulation and decrease portal hypertension and rifaximin modulates the gut microbiome and might prevent bacterial translocation in patients with cirrhosis. Therefore, this drug combination might be of therapeutic benefit in patients with decompensated cirrhosis. However, there is concern regarding the safety of statins in patients with decompensated cirrhosis. We assessed the safety of two different doses of simvastatin, in combination with rifaximin, in patients with decompensated cirrhosis. // METHODS: We did a double-blind, randomised, placebo-controlled, phase 2 trial in patients with decompensated cirrhosis and moderate-to-severe liver failure from nine university hospitals in six European countries (Italy, France, Holland, Germany, the UK, and Spain). Patients older than 18 years with Child-Pugh class B or C disease were eligible. We randomly assigned patients (1:1:1) to receive either simvastatin 40 mg/day plus rifaximin 1200 mg/day, simvastatin 20 mg/day plus rifaximin 1200 mg/day, or placebo of both medications for 12 weeks. Randomisation was stratified according to Child-Pugh class (B vs C) and restricted using blocks of multiples of three. The primary endpoint was development of liver or muscle toxicity, as defined by changes in liver aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), alkaline phosphastase, and creatine kinase. The study is registered with the European Union Clinical Trials Register, 2016-004499-23, and with ClinicalTrials.gov, NCT03150459. // FINDINGS: The study recruitment period was between July 28, 2017, and Jan 2, 2018. Follow-up finished on March 12, 2018. 50 patients were randomly assigned to simvastatin 40 mg/day plus rifaximin 1200 mg/day (n=18), simvastatin 20 mg/day plus rifaximin 1200 mg/day (n=16), or placebo of both medications (n=16). Six patients (two from each group) were excluded. Therefore, the full analysis set included 44 patients (16 in the simvastatin 40 mg/day plus rifaximin 1200 mg/day group, 14 in the simvastatin 20 mg/day plus rifaximin mg/day group, and 14 in the placebo group). After a safety analyses when the first ten patients completed treatment, treatment was stopped prematurely in the simvastatin 40 mg/day plus rifaximin group due to recommendations by the data safety monitoring board. Patients in the simvastatin 40 mg/day plus rifaximin group showed a significant increase in AST and ALT compared with the placebo group (mean differences between the groups at the end of treatment for AST 130 IU/L [95% CI 54 to 205; p=0·0009] and for ALT 61 IU/L [22 to 100; p=0·0025]. We observed no significant differences at 12 weeks in AST and ALT between the simvastatin 20 mg/day plus rifaximin and placebo group (for AST -14 IU/L [-91 to 64; p=0·728] and for ALT -8 IU/L [-49 to 33; p=0·698]). We observed no significant differences in alkaline phosphatase between the the simvastatin 40 mg/day plus rifaximin or the simvastatin 20 mg/day plus rifaximin groups compared with placebo. Patients in the simvastatin 40 mg/day plus rifaximin group showed an increase in creatine kinase at the end of treatment compared with patients in the placebo group (1009 IU/L [208 to 1809]; p=0·014). We observed no significant changes in creatine kinase in the simvastatin 20 mg/day plus rifaximin group (4·2 IU/L [-804 to 813]; p=0·992). Three (19%) patients in the simvastatin 40 mg/day group developed liver and muscle toxicity consistent with rhabdomyolysis. The number of patients who stopped treatment because of adverse events was significantly higher in the simvastatin 40 mg/day plus rifaximin group (nine [56%] of 16 patients) compared with the other two groups (two [14%] of 14 for both groups; p=0·017). There were no serious unexpected adverse reactions reported during the study. // INTERPRETATION: Treatment with simvastatin 40 mg/day plus rifaximin in patients with decompensated cirrhosis was associated with a significant increase in adverse events requiring treatment withdrawal, particularly rhabdomyolysis, compared with simvastatin 20 mg/day plus rifaximin. We recommend simvastatin 20 mg/day as the dose to be used in studies investigating the role of statins in patients with decompensated cirrhosis. //FUNDING: Horizon 20/20 European programme