Detection of non-consumptive effects of predation and intraspecific aggression in fire salamander larvae: Environmental issues

The identification of injury causes may reveal important insights on the factors that influence intra and interspecific predation pressures. In this study we evaluated the proportion of injuries occurring in fire salamander larvae (Salamandra salamandra) in caves and epigean springs to understand the factors determining non-consumptive effects that may affect larval survival. We surveyed 25 sites (13 cave pools, 12 spring pools) during the day. We applied two consecutive removal samplings to collect fire salamander larvae and examined every removed larva to detect if it had injuries and we evaluated the proportion of the injured larvae on the total number of collected larvae. For each site we recorded different environmental variables including predator occurrence and prey density. The proportion of injured larvae was significantly linked only to predators occurrence. Our results show that interspecific predation pressure is a major source of non-consumptive effects that may affect larval survival Overall, our study underlines the role that environmental features may play on the non-consumptive effects of selective pressures that affect larval survival. Predator occurrence determines the levels of non-consumptive effects and larval survival across their developmental cycle. These results deriving from a field survey could furnish useful insights for further experimental studies

CAN METABOLIC SYNDROME AFFECT THE EFFICACY OUTCOMES OF COMBINATION THERAPY WITH DAILY TADALAFIL 5MG PLUS TAMSULOSIN 0.4MG IN MEN WITH LUTS AND ED?

INTRODUCTION AND OBJECTIVE: Metabolic Syndrome (METS) has a high prevalence (26.5%–55.6%) in men with LUTS and erectile dysfunction (ED). Daily tadalafil 5mg intake is currently recognized as an effective pharmacological treatment for male LUTS, alone or in combination with alpha-lithics such as tamsulosin 0,4mg, ensuring a greater LUTS relieve. Aim of this study is to assess if METS could affect the efficacy of combination therapy with daily tadalafil 5mg plus tamsulosin 0,4mg in men with LUTS and ED. METHODS: Across 12 months, fifty consecutive patients aged >40 to 80 years, with moderate to severe LUTS (IPSS >7) and mild to severe ED (IIEF-5 <22) were enrolled and treated with the previous combination therapy for 12 weeks. The assessment of patients included age, body mass index (BMI), METS features - waist circumference (WC), blood pressure, clinical laboratory parameters- digital rectal examination, IPSS, OABq, uroflowmetry and postvoid residual (PVR) volume, IIEF-5. METS was defined according to NCEP ATP III. Differences were calculated by unpaired sample t-test at baseline and 12 weeks. The analysis of variance (ANOVA) was used for between-group differences. RESULTS: Among 50 patients enrolled, 31 (62.0%) had METS. Mean age was similar with 65.5 years (9.1) in patients without METS and 67.1 years (7.2) in METS patients, p=0.133. Baseline IPSS, OAB-q and IPSS QoL were significantly higher in patients with METS (p<0.05), while IIEF was higher in patients without METS (p=0.039) at baseline (Table1). After 3 months of combination therapy, IIEF, total IPSS and subscores, OAB-q and Qmax significantly improved in both groups. DeltaIPSS, deltaQMax and deltaIIEF were similar between groups (p>0.05). However, total IPSS, IPSS QoL, IPSS Voiding and IPSS Storage were significantly better at the end of the trial in men without METS. Conversely, 12wks IIEF was similar in patients with or without METS (16.3 vs 17.7 p=0.238) (Table2). CONCLUSIONS: Tadalafil plus tamsulosin combi therapy represents an effective LUTS treatment in male, independently from METS. Despite a similar improvement of LUTS (delta), patients without METS obtained a significantly better LUTS relieve. Interestingly, the efficacy in ED was greater in men with METS and, at the end of trial, IEEF-5 scores were similar in the two groups

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Precision measurement of the neutrino velocity with the ICARUS detector in the CNGS beam

During May 2012, the CERN-CNGS neutrino beam has been operated for two weeks for a total of 1.8 10^17 pot in bunched mode, with a 3 ns narrow width proton beam bunches, separated by 100 ns. This tightly bunched beam structure allows a very accurate time of flight measurement of neutrinos from CERN to LNGS on an event-by-event basis. Both the ICARUS-T600 PMT-DAQ and the CERN-LNGS timing synchronization have been substantially improved for this campaign, taking ad-vantage of additional independent GPS receivers, both at CERN and LNGS as well as of the deployment of the "White Rabbit" protocol both at CERN and LNGS. The ICARUS-T600 detector has collected 25 beam-associated events; the corresponding time of flight has been accurately evaluated, using all different time synchronization paths. The measured neutrino time of flight is compatible with the arrival of all events with speed equivalent to the one of light: the difference between the expected value based on the speed of light and the measured value is tof_c - tof_nu = (0.10 \pm 0.67stat. \pm 2.39syst.) ns. This result is in agreement with the value previously reported by the ICARUS collaboration, tof_c - tof_nu = (0.3 \pm 4.9stat. \pm 9.0syst.) ns, but with improved statistical and systematic errors.Comment: 21 pages, 13 figures, 1 tabl

Measurement of CNGS muon neutrino speed with Borexino

We have measured the speed of muon neutrinos with the Borexino detector using short-bunch CNGS beams. The final result for the difference in time-of-flight between a =17 GeV muon neutrino and a particle moving at the speed of light in vacuum is {\delta}t = 0.8 \pm 0.7stat \pm 2.9sys ns, well consistent with zero.Comment: 6 pages, 5 figure

Clinical, immunological, and molecular features of typical and atypical severe combined immunodeficiency: Report of the italian primary immunodeficiency network

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented

De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions.

Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very similar and unique clinical presentation of childhood-onset chorea and characteristic brain MRI showing symmetrical bilateral striatal lesions. All individuals were identified to carry a de novo heterozygous mutation in PDE10A (c.898T>C [p.Phe300Leu] in two individuals and c.1000T>C [p.Phe334Leu] in one individual), encoding a phosphodiesterase highly and selectively present in MSNs. PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. In silico modeling showed that the altered residues are located deep in the binding pocket, where they are likely to alter cAMP binding properties. In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. The identification of PDE10A mutations as a cause of chorea further motivates the study of cAMP signaling in MSNs and highlights the crucial role of striatal cAMP signaling in the regulation of basal ganglia circuitry. Pharmacological modulation of this pathway could offer promising etiologically targeted treatments for chorea and other hyperkinetic movement disorders