Extracellular Pax6 Regulates Tangential Cajal-Retzius Cell Migration in the Developing Mouse Neocortex.

The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.

Micro-CT evaluation of two different root canal filling techniques.

OBJECTIVE: The aim of this study was to compare the frequency and volume of voids in root canals obturated with two different filling techniques using micro-computed tomography (micro-CT). MATERIALS AND METHODS: Forty single-rooted permanent teeth were selected and decoronated. The roots were instrumented with WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) to a large size until working length and irrigated with 5.25% sodium hypochlorite and 17% EDTA. Then, the samples were filled using a single-cone (n = 20) or the GuttaCore technique (n = 20). The presence and volume (mm3) of voids (internal, external, and combined) was calculated in the coronal, medium, and apical thirds using micro-CT (SkyScan 1072; SkyScan, Kartuizersweg, Belgium). Statistical analyses were performed using the χ2-test and Kruskal-Wallis tests (p<0.05). RESULTS: The frequency and total volume of voids in the middle third and the external voids in the coronal third were statistically significant (p<0.05). Within the same group, both techniques (single-cone and Guttacore) showed statistically significant differences in external and internal voids (p<0.05). CONCLUSIONS: The GuttaCore technique showed better results in the coronal and medium thirds than the single-cone technique. Our results showed that the single-cone and GuttaCore techniques were comparable in the apical third (p>0.05).

A multi-disciplinary approach to evaluate pluvial floods risk under changing climate: The case study of the municipality of Venice (Italy).

Global climate change is likely to pose increasing threats in nearly all sectors and across all sub-regions worldwide (IPCC, 2014). Particularly, extreme weather events (e.g. heavy precipitations), together with changing exposure and vulnerability patterns, are expected to increase the damaging effect of storms, pluvial floods and coastal flooding. Developing climate and adaptation services for local planners and decision makers is becoming essential to transfer and communicate sound scientific knowledge about climate related risks and foster the development of national, regional and local adaptation strategies. In order to analyze the effect of climate change on pluvial flood risk and advice adaptation planning, a Regional Risk Assessment (RRA) methodology was developed and applied to the urban territory of the municipality of Venice. Based on the integrated analysis of hazard, exposure, vulnerability and risk, RRA allows identifying and prioritizing targets and sub-areas that are more likely to be affected by pluvial flood risk due to heavy precipitation events in the future scenario 2041-2050. From the early stages of its development and application, the RRA followed a bottom-up approach taking into account the requests, knowledge and perspectives of local stakeholders of the North Adriatic region by means of interactive workshops, surveys and discussions. Results of the analysis showed that all targets (i.e. residential, commercial-industrial areas and infrastructures) are vulnerable to pluvial floods due to the high impermeability and low slope of the topography. The spatial pattern of risk mostly reflects the distribution of the hazard and the districts with the higher percentage of receptors' surface in the higher risk classes (i.e. very high, high and medium) are Lido-Pellestrina and Marghera. The paper discusses how risk-based maps and statistics integrate scientific and local knowledge with the final aim to mainstream climate adaptation in the development of risk mitigation and urban plans.

Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors.

Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development.

Removal of humic substances from water by means of calcium-ion-enriched natural zeolites.

The ability of the natural zeolited Neapolitan Yellow Tuff (NYT) enriched with calcium ions to remove humic acids from water was evaluated by batch adsorption equilibrium tests and dynamic experiments carried out by percolating humic acid solutions through a small NYT column (breakthrough curves). Under the experimental condition explored, the sorption capacity increases with the ionic strength and has the highest value at pH 7.4. The partition coefficient for a low concentration of humic acid ([humic acid] --> 0), at pH 7.4 in 0.01 M sodium chloride, was approximately 1000 L/kg, versus the value of approximately 100 L/kg in the absence of the alkaline metal salt. Therefore, after humic acids have been adsorbed in a column filled with the calcium-ion-enriched tuff, a reduction of the salt concentration in the ongoing solution enhances the release of the adsorbed material. These findings show that NYT can be used for the removal of humic acids from water.

Importance of reperfusion on thromboxane A2 metabolite excretion after thrombolysis.

Fibrinolytic therapy is a major advance in the treatment of coronary artery disease. A marked elevation in plasma and urinary metabolites of thromboxane A2 (TXA2) after administration of thrombolytic therapy has been observed and has been related to a direct effect of thrombolytic drugs on platelets. To test this hypothesis we evaluated the 11-dehydro-thromboxane B2 (11-d-TXB2) level, as an index of platelet activation, in 20 healthy subjects and in 30 patients with acute myocardial infarction (AMI). Patients with infarction received streptokinase (n = 8), recombinant tissue-type plasminogen activator (rt-PA) (n = 8), or thrombolytic therapy preceded by acetylsalicylic acid (n = 7) or were treated without thrombolytic therapy (n = 7). The urinary 11-d-TXB2 level in healthy control subjects was 327 +/- 126 pg/mg creatinine. A significant increase was observed in patients with AMI with no difference between those who received no thrombolytic therapy (673 +/- 283 pg/mg creatinine in the first 12 hours) and those who received streptokinase (833 +/- 613 pg/mg creatinine) or rt-PA (836 +/- 653 pg/mg creatinine). Patients pretreated with acetylsalicylic acid had urinary 11-d-TXB2 values ranging between 361 and 155 pg/mg creatinine. A significant difference in 11-d-TXB2 values was observed only when patients who were reperfused were separated from those who remained occluded according to angiographic criteria (1085 +/- 498 vs 391 +/- 227 pg/mg creatinine in the first 12 hours, p less than 0.001). We conclude that reperfusion and not thrombolytic agents per se appears to be the factor that induces platelet activation and consequently facilitates reocclusion.

[rTPA and streptokinase in acute myocardial infarct. Clinical instrumental evaluation of the 2 treatments]. / rTPA e streptokinasi nell'infarto miocardico acuto. Valutazione clinico strumentale dei due trattamenti.

Fifty-four patients with acute myocardial infarction were treated with thrombolytic therapy (27 with rTPA and 27 with streptokinase). In all the subjects CK was monitored (every 3 hours) and ergometric test, echocardiogram, and 24 hours holter ecg were performed in the pre-discharge period. In 22 of the patients, coronary angiography was also performed. No differences were shown between the two groups of patients as regards CK values and ejection fraction. Repetitive ventricular premature beats were registered without difference between the two groups (23% in patients treated with SK and 18% in the patients treated with rTPA). No bleeding events were shown in the patients treated with rTPA without calciparin. On the other hand no difference there was between patients treated with rTPA + calciparin and patients treated with SK with or without calciparin.

Circadian variation of ventricular tachycardia in acute myocardial infarction.

Circadian rhythms have been described both for acute myocardial infarction (AMI) and sudden death. In this study the diurnal distribution of ventricular tachycardia (VT) in patients with AMI was analyzed. Ninety-four AMI patients with greater than or equal to 1 VT on Holter electrocardiographic monitoring who were not taking antiarrhythmic drugs were studied. Forty-seven patients had a recent AMI (group A) and 47 an old AMI (group B). Chronobiologic analysis was made by single cosinor method. There were 157 VTs (mean 1.67 VTs/patient, range 1 to 10) in the 94 patients: 70 in group A and 87 in group B. A significant circadian rhythm of VT was found in the total population with acrophase at 2:29 P.M. The hourly distribution of VT showed a tendency to bimodality, which seemed due to a different time of peak VT occurrence in group A (significant rhythm with acrophase at 4:40 P.M.) and group B (significant rhythm with acrophase at 12:39 P.M.). Thus, the hourly VT frequency in patients with AMI has a significant circadian variation with the highest occurrence in the awake hours, similar to the rhythms described for AMI and sudden death.

Circadian rhythm of ventricular tachycardia.

A 24-hr electrocardiographic monitoring was performed in 406 patients (297 with ischemic heart disease). Forty-one episodes of ventricular tachycardia were detected in 32 subjects (7.88%). The average rate of tachycardia was 127.4 (range 180-65). No correlation was observed between the rate of ventricular tachycardia and the heart rate 30, 20, and 10 min before and at the moment of the episode. A circadian rhythm of all the episodes was demonstrated, with an acrophase at 1102 hr. A different acrophase was observed for the QT interval. No significant rhythm was observed for premature ventricular beats in the patients with ventricular tachycardia. The circadian variation of tachycardia suggests that this arrhythmia is related to sympathetic tone, but it will require further studies with a larger number of patients with ventricular tachycardia to clarify this problem.

Assessment of left atrial dimensions by cross sectional echocardiography in patients with mitral valve disease.

Left atrial dimensions were measured using cross sectional echocardiography in 37 patients with mitral valve disease and 30 normal subjects of similar ages. The anteroposterior (AP), superior-inferior (SI), and medial-lateral (ML) left atrial dimensions were determined at the end of ventricular systole using parasternal long and short axis and apical four chamber views (for SIa and MLa). To assess the reliability of these measurements cross sectional echocardiographic and angiographic left atrial volumes were compared in 19 patients with mitral valve disease, giving an excellent correlation. A moderate correlation was found between the anteroposterior dimension of the left atrium obtained using M mode echocardiography and that obtained using the parasternal short axis and long axis projections. In normal subjects a good correlation was found between SI and ML dimensions, while a lower correlation was found between SI and AP, and ML and AP dimensions. The SI dimension was the major axis of the left atrium and AP dimension the minor axis. In patients with mitral valve disease a good correlation was found between SI and ML dimensions, while SI and ML dimensions had a low correlation with AP dimensions. The AP dimension was the minor axis of the left atrium, while the SI and ML dimensions were not significantly different. All left atrial dimensions were significantly greater in patients with mitral valve disease than in normal subjects. Of 30 patients with at least one dimension increased, all three dimensions were abnormal in 16, two dimensions were increased in 10, and only one dimension was increased in four. AP, SI, and ML dimensions were abnormal in 25, 20, and 27 patients, respectively. Cross sectional echocardiography may provide a reliable estimate of left atrial dimensions. In patients with mitral valve disease a thorough examination of the left atrium using multiple cross sectional views is necessary to detect asymmetric left atrial enlargement and to measure the degree of left atrial dilatation.

Significance of high voltage QRS anterior forces in young asymptomatic adults. Evaluation by wide-angle two-dimensional echocardiography.

Thirteen asymptomatic adults less than 40 years old who showed tall right precordial R waves on the ECG were examined by VCG, M-mode and two-dimensional echocardiography (2D Echo). Common causes of QRS anterior displacement, such as right ventricular enlargement or right bundle branch block, were excluded in each subject. Although each subject was normal at physical examination, 2D Echo revealed areas of left ventricular hypertrophy in eight of these 13 subjects. Four had a prevailing hypertrophy of the basal portion of the interventricular septum, three had an isolated apical hypertrophy, and one had a diffuse concentric left ventricular hypertrophy. Results were normal in five cases. 2D Echo classification was confirmed by heart catheterization findings, when available. The subjects with asymmetric septal hypertrophy showed low-voltage QRS leftward forces on the ECG and VCG. ECGs and VCGs were not useful in differentiating the subjects with atypically distributed left ventricular hypertrophy from the normals: high-voltage QRS leftward forces and T wave abnormalities were evident in some subjects of both groups. Tall right precordial R waves may constitute a marker of hypertrophic cardiomyopathy in asymptomatic young adults. 2D Echo is useful to exactly classify these subjects.