Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice

Background Gain-of-function missense mutations in the alpha(1A) subunit of neuronal Ca(V)2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic transmission and a higher susceptibility to cortical spreading depolarization. It is now well established that neurons signal to surrounding glial cells, namely astrocytes and microglia, in the central nervous system, which in turn become activated and in pathological conditions can sustain neuroinflammation. We and others previously demonstrated an increased activation of pro-algogenic pathways, paralleled by augmented macrophage infiltration, in both isolated trigeminal ganglia and mixed trigeminal ganglion neuron-satellite glial cell cultures of FHM1 mutant mice. Hence, we hypothesize that astrocyte and microglia activation may occur in parallel in the central nervous system. Methods We have evaluated signs of reactive glia in brains from naive FHM1 mutant mice in comparison with wild type animals by immunohistochemistry and Western blotting. Results Here we show for the first time signs of reactive astrogliosis and microglia activation in the naive FHM1 mutant mouse brain. Conclusions Our data reinforce the involvement of glial cells in migraine, and suggest that modulating such activation may represent an innovative approach to reduce pathology

Flunisolide Decreases Exhaled Nitric Oxide and Nitrotyrosine Levels in Asthmatic Children

Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects

Alert for upper airway stenosis in a child with fixed obstructive airways pattern at spirometry

gan et al. [1] reported an interesting case of 40-year- old female affected by Granulomatosis with Polyangiitis (GPA) that developed a Subglottic Stenosis (SS) in the remission period. Patient reported hoarseness and developed stridor. Laryngoscopy con rmed constriction in the subglottic region. Although life-threatening and plays an important role in morbidity, patients may show progressive Subglottic Stenosis (SS) even in the remission period. Authors argue that it can be the rst and only symptom of the SS disease despite being very rare

Reflux and dyspeptic symptom patterns in patients with non erosive reflux disease (NERD) subclassified using 24-hour ambulatory intraluminal pH-Impedance

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis

Surveillance for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: Universal or Selective?

Hepatocellular carcinoma (HCC), the most frequent primary liver cancer, is the sixth most common cancer, the fourth leading cause of cancer-related deaths worldwide, and accounts globally for about 800,000 deaths/year. Early detection of HCC is of pivotal importance as it is associated with improved survival and the ability to apply curative treatments. Chronic liver diseases, and in particular cirrhosis, are the main risk factors for HCC, but the etiology of liver disease is rapidly changing due to improvements in the prevention and treatment of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) infections and to the rising incidence of the metabolic syndrome, of which non-alcoholic fatty liver (NAFLD) is a manifestation. NAFLD is now a recognized and rapidly increasing cause of cirrhosis and HCC. Indeed, the most recent guidelines for NAFLD management recommend screening for HCC in patients with established cirrhosis. Screening in NAFLD patients without cirrhosis is not recommended; however, the prevalence of HCC in this group of NAFLD patients has been reported to be as high as 38%, a proportion significantly higher than the one observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Unfortunately, solid data regarding the risk stratification of patients with non-cirrhotic NAFLD who might best benefit from HCC surveillance are scarce, and specific recommendations in this field are urgently needed due to the increasing NAFLD epidemic, at least in Western countries. To further complicate matters, liver ultrasonography, which represents the current standard for HCC surveillance, has a decreased diagnostic accuracy in patients with NAFLD, and therefore disease-specific surveillance tools will be required for the early identification of HCC in this population. In this review, we summarize the most recent evidence on the epidemiology and risk factors for HCC in patients with NAFLD, with and without cirrhosis, and the evidence supporting surveillance for early HCC detection in these patients, reviewing the potential limitations of currently recommended surveillance strategies, and assessing data on the accuracy of potential new screening tools. At this stage it is difficult to propose general recommendations, and best clinical judgement should be exercised, based on the profile of risk factors specific to each patient

Do grade II ankle sprains have chronic effects on the functional ability of ballet dancers performing single-leg flat-foot stance? An observational cross-sectional study

Ballet dancers have a higher risk than the general population of ankle sprains. Ankle proprioception is of the utmost importance for executing static and dynamic positions typical of ballet dancing. Ankle sprains can create changes in functional ability that may affect ballet performance. The aim of this cross-sectional observational study is to evaluate if non-professional ballet dancers that were previously injured with a grade II ankle sprain carry a long-term stability deficit in ballet specific positions (pass\ue9, arabesque) and in single-leg flat-foot stance, thereby affecting ballet performance. We enrolled 22 amateur female ballet dancers, 11 who previously had a grade II ankle injury and 11 who had no history of ankle injury. Stabilometric data (Center of Pressure Speed and Elipse Area) were assessed with the postural electronic multisensory baropodometer in normal, arabesque, and pass\ue8 positions with both open and closed eyes. Using an unpaired t-test, we compared healthy and pathological feet of the ankle injury group for a standard monopodalic position and two ballet-specific positions. No difference between pathological and healthy feet of non-professional ballet dancers who suffered grade II ankle injury was detected. According to the parameters considered in this study, grade II ankle sprains seem to have a favorable prognosis in the sample that we evaluated

Investigating the possibility of leakage detection in water distribution networks using cosmic ray neutrons in the thermal region

Water distribution systems can experience high levels of leakage, originating from different sources, such as deterioration due to aging of pipes and fittings, material defects, and corrosion. In addition to causing financial losses and supply problems, leakages in treated water distribution also represent a risk for public health. Despite several techniques for leak detection are already available, there is still a lot of interest in new non-invasive approaches, especially for scenarios where acoustic techniques struggle, such as in noisy environmental conditions. In this work we investigated the possibility of using cosmic ray (CR) neutrons for the detection of underground leakages in water distribution networks, by exploiting the difference in the above ground thermal neutron flux between dry and wet soil conditions. The potential of the technique has been assessed by means of an extensive set of Monte Carlo simulations based on GEANT4, involving realistic scenarios based on the Italian aqueduct design guidelines. Simulation studies focused on sandy soils and results suggest that a significative signal, associated with a leakage, could be detected with a data-taking lasting from a few minutes to a half-hour, depending on the environmental soil moisture, the leaking water distribution in soil, and the soil chemical composition. Finally, a brief description of a new portable and low-cost detector for thermal neutrons, currently under commission, is also presented