Laryngopharyngeal reflux and idiopathic vocal fold scars.

peer reviewedReflusso laringofaringeo e cicatrici idiopatiche delle corde vocali

HIV-1 tat protein enters dysfunctional endothelial cells via integrins and renders them permissive to virus replication

Previous work has shown that the Tat protein of Human Immunodeficiency Virus (HIV)-1 is released by acutely infected cells in a biologically active form and enters dendritic cells upon the binding of its arginine-glycine-aspartic acid (RGD) domain to the α5β1, αvβ3, and αvβ5 integrins. The up-regulation/activation of these integrins occurs in endothelial cells exposed to inflammatory cytokines that are increased in HIV-infected individuals, leading to endothelial cell dysfunction. Here, we show that inflammatory cytokine-activated endothelial cells selectively bind and rapidly take up nano-micromolar concentrations of Tat, as determined by flow cytometry. Protein oxidation and low temperatures reduce Tat entry, suggesting a conformation- and energy-dependent process. Consistently, Tat entry is competed out by RGD-Tat peptides or integrin natural ligands, and it is blocked by anti-α5β1, -αvβ3, and -αvβ5 antibodies. Moreover, modelling-docking calculations identify a low-energy Tat-αvβ3 integrin complex in which Tat makes contacts with both the αv and β3 chains. It is noteworthy that internalized Tat induces HIV replication in inflammatory cytokine-treated, but not untreated, endothelial cells. Thus, endothelial cell dysfunction driven by inflammatory cytokines renders the vascular system a target of Tat, which makes endothelial cells permissive to HIV replication, adding a further layer of complexity to functionally cure and/or eradicate HIV infection

Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Abstract Background Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. Results Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing loss patients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup. Conclusions In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations

Original Article

The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism

Stapedotomy: Is the color of the footplate important in the choice of the type of perforator?

OBJECTIVE: To valuate the influence of the color of footplate in the choice of the type of perforator. STUDY DESIGN: Prospective study. Level of Evidence 1b. SETTINGS: Single hospital study in Avellino, Italy. SUBJECTS AND METHODS: From the first of September 2008 to the 30th of June 2009, we considered 83 patients affected by otosclerosis. Patients were divided into 2 groups under footplate perforator used. In the group A, manual perforators (the more traumatic drills) were used. In group B, CO2 laser (the less traumatic drill) was used.The 2 groups under the color of visible portion of the footplate before removing the stapes superstructure were divided in 2 subgroups. Group IA includes 33 blue footplates and Group IIA 10 white footplates. Group IB includes 30 blue footplates and Group IIB 10 white footplates. We estimated whether there is statistical correlation between type of perforator, incidence of footplate complications, and color of footplate. RESULTS: In group IA, we had 0 complications. In group IB, we had 0 complications. In group IIA, we had 7 complications. In group IIB, we had 2 complications.Comparison of incidence of footplate complications showed no statistical significance between group IA and IB and statistical significance between group IIA and IIB. CONCLUSION: The footplate color is important in the choice of the type of perforator. © 2011, Otology &Neurotology, Inc

Spatio-temporal hotspots and application on a disease analysis case via GIS

Hotspot analysis is a spatial analysis that uses cluster techniques for determining areas with elevated concentrations of localized events. We use the consolidated Extended Fuzzy C-Means algorithm to determine the hotspot areas on the map as circles, moreover the advantages of this technique are the linear computational complexity, the robustness to noise and outliers, the automatic determination of the optimal number C of clusters (in the classical FCM algorithm C is chosen a priori). Furthermore it prevents the problem of shifting the clusters with low density area of data points in areas with higher density of such points. We apply this method to study the spatio-temporal variations of the hotspot areas by testing this process on a specific disease problem, precisely we have clusterized 5,000 point-events correspondent to cases of brain cancer detected in the state of New Mexico from 1973 to 1991. We also show that the same results are obtained by using the Extended Gustafson– Kessel algorithm which gives elliptical clusters. We have implemented both algorithms in a Geographic Information System environment. Thus we establish the areas which seem not interested from the incidence of the disease and those areas in which the phenomenon appears to be temporarily attenuated either increased or constant or quite disappeared