Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report

Background We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). Case presentation A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. Conclusions This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway

Giving meaning to alternative methods to animal testing

The 3 rd edition of the advanced theoretical-training course \u201c Giving meaning to alternative methods to animal testing \u201d was held in Genoa on July 6-7, 2017. The theoretical modules included talks by specialists from companies engaged in the field of advanced in vitro technologies, who offered participants the possibility to try out their technologies in the training modules

Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process

Macrosoma hedylaria (Warren, 1894): A new record of Hedylidae Guenée, 1858 from Misiones, Argentina (Lepidoptera: Papilionoidea)

En este trabajo se dan a conocer dos ejemplares de M. hedylaria recolectados en Misiones.Fil: Núñez Bustos, Ezequiel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Penco, Fernando C.. Fundación de Historia Natural Félix de Azara; Argentin

Two-colour generation in a chirped seeded Free-Electron Laser

We present the experimental demonstration of a method for generating two spectrally and temporally separated pulses by an externally seeded, single-pass free-electron laser operating in the extreme-ultraviolet spectral range. Our results, collected on the FERMI@Elettra facility and confirmed by numerical simulations, demonstrate the possibility of controlling both the spectral and temporal features of the generated pulses. A free-electron laser operated in this mode becomes a suitable light source for jitter-free, two-colour pump-probe experiments

Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties

Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having amyloid properties. Here we have purified full-length TDP-43 (FL TDP-43) and its C-terminal domain (Ct TDP-43) to investigate the morphological, structural and tinctorial features of aggregates formed in vitro by them at pH 7.4 and 37 °C. AFM images indicate that both protein variants show a tendency to form filaments. Moreover, we show that both FL TDP-43 and Ct TDP-43 filaments possess a largely disordered secondary structure, as ascertained by far-UV circular dichroism and Fourier transform infra-red spectroscopy, do not bind Congo red and induce a very weak increase of thioflavin T fluorescence, indicating the absence of a clear amyloid-like signature

Role of endogenous opioids on nociceptive threshold in patients with exercise-induced myocardial ischemia.

To evaluate whether endogenous opioids (EO) play a role in the perception of anginal pain, a randomized double blind clinical trial, using naloxone (N) and placebo (P) and measuring beta-endorphin (beta-ep) plasma levels, was performed. We studied 10 patients with angiographically assessed coronary artery disease (CAD) and stable exercise-induced myocardial ischemia (established by 2 preliminary bicycle ergometric tests) of whom 5 symptomatic (SYM) and 5 asymptomatic (ASYM) and 5 subjects without CAD as a control group (CON). On a third exercise test the beta-ep plasma level (fmol/ml) was measured at rest (SYM 5.4 +/- 2.3 vs ASYM 7.2 +/- 2.3 vs CON 6.8 +/- 2.6, NS), at peak exercise (SYM 4.4 +/- 1.8 vs ASYM 8.0 +/- 4.2 and vs CON 6.2 +/- 2.7, NS) and during recovery (SYM 7.5 +/- 4.2 vs ASYM 7.2 +/- 3.0 vs CON 6.7 +/- 2.5, NS). On 2 subsequent tests patients received N (0.2 mg/kg) or P intravenously and chest pain was evaluated on an analogue scale (score from 1 to 10). After N compared to P we observed: an increased perception of chest pain in SYM (6.8 +/- 1.5 vs 4.2 +/- 1.0; p less than 0.01) without significant changes of the ischemic threshold (total work, heart rate-blood pressure product, ST segment changes, 2D-echocardiographic wall motion abnormalities); no modifications in ASYM and CON.(ABSTRACT TRUNCATED AT 250 WORDS

Transesophageal dipyridamole echocardiography for diagnosis of coronary artery disease.

The value of transthoracic dipyridamole echocardiography has been extensively documented. However, in some patients, because of a poor acoustic window, the rest transthoracic examination is not always feasible and the transesophageal approach is more convenient. Therefore, transesophageal echocardiography with high dose dipyridamole (up to 0.84 mg/kg body weight over 10 min) was performed in 32 patients in whom the transthoracic dipyridamole test either was not feasible (n = 29) or yielded ambiguous results (n = 3). The transesophageal echocardiographic test results were considered abnormal when new dipyridamole-induced regional wall motion abnormalities were observed. All 32 patients underwent coronary angiography; significant coronary artery disease was defined as greater than or equal to 70% lumen diameter narrowing in at least one major vessel. All patients also performed a bicycle exercise test 1 day before transesophageal dipyridamole echocardiography. Transesophageal stress studies were completed in all patients, with a maximal imaging time (in tests with a negative result) of 20 min. No side effects or intolerance to drug or transducer was observed. The left ventricle was always visualized in the four-chamber and transgastric short-axis views. High quality two-dimensional echocardiographic images were obtained in all patients both at rest and at peak dipyridamole infusion and were digitally analyzed in a quad-screen format. Coronary angiography showed coronary artery obstruction in 24 patients: 6 had single-, 9 double- and 9 triple-vessel disease. The transesophageal dipyridamole test showed a specificity of 100% and an overall sensitivity of 92%. The sensitivity of this test for single-, double- and triple-vessel disease was 67%, 100% and 100%, respectivel

Different gene expression modulation is the major effect fue to shear stress and stent application in huvecs model: preliminary results

Although it is known that disturbed shear stress may cause endothelial damage, the mechanism by which a stent procedure may affect the endothelium is not yet fully clarify. We present the preliminary data on gene expression analysis of human endothelial cells in a laminar flow bioreactor (LFB) system submitted to different physical (flow changes) and/or mechanical (stent application) stimuli. Our preliminary results show that low shear stress together with stent procedure are the experimental conditions that mainly modulate the highest number of genes in human endothelial model. Those genes belong to pathways specifically involved in the endothelial dysfunctio

Context Dependence, MOPs,WHIMs and procedures Recanati and Kaplan on Cognitive Aspects in Semantics

After presenting Kripke’s criticism to Frege’s ideas on context dependence of thoughts, I present two recent attempts of considering cognitive aspects of context dependent expressions inside a truth conditional pragmatics or semantics: Recanati’s non-descriptive modes of presentation (MOPs) and Kaplan’s ways of having in mind (WHIMs). After analysing the two attempts and verifying which answers they should give to the problem discussed by Kripke, I suggest a possible interpretation of these attempts: to insert a procedural or algorithmic level in semantic representations of indexicals. That a function may be computed by different procedures might suggest new possibilities of integrating contextual cognitive aspects in model theoretic semanti