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Glaucoma is an optic neuropathy, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

AbstractThis note concerns the open channel flow problem. The flow is assumed to be steady (with constant discharge), two-dimensional (with non-hydrostatic pressure distribution), without both wave breaking and sediment transport. The flow problem consists in finding the location of the free surface, and the velocity and pressure fields. The problem solution is obtained by a hybrid model which incorporates the dissipation in potential flows. In order to set up the model, this note proposes a new Picard iteration for the potential velocity field. By coupling approximate expressions for the velocity field to dynamic equations, the flow problem is reduced to one of solving a nonlinear ordinary differential equation. To illustrate the model validation, numerical simulations are performed for open channel flow over curved bottom, and the free overfall problem. In terms of free surface location and bottom pressure profile, the obtained results are in good agreement with data in literature.

To evaluate the wear of new rotary instruments produced via electro discharge machining and to test their fatigue resistance.

Thyroid Associated Ophthalmopathy (TAO) is a complex pathology to treat and a considerable threat for Graves' Disease (GD) patients. Thus, there is great interest to find tools able to predict the onset and prognosis of TAO. Chronic inflamed tissues are characterized by tissue damage and recruitment of cells from the bloodstream, events that can lead to self-antigen exposure and induce autoimmune phenomena. In this study, we determined whether the occurrence of antibody anti-extracellular matrix (ECM) molecules [Collagen CI, CIII, CIV, CV, laminin (LM) and fibronectin, (FN)], anti-smooth muscle (ASM), anti-nuclear antigen (ANA), anti-ribonucleoprotein (RNP) and anti-thyroid-stimulating hormone (TSH) receptor (TRAbs) were associated with TAO in GD patients. We analyzed serum of 50 patients affected by GD, 24 of whom were affected by TAO, and 40 healthy donors (HD). The occurrence of TRAbs or ANA, anti-SM and anti-RNP antibodies did not allow to discriminate TAO+ from TAO- GD patients. Among the 24 TAO+ and 26 TAO- patients, 15/24 and 17/26 displayed TRAbs, respectively. None of the GD patients displayed anti-RNP antibodies, while 20/24 TAO+ and 17/26 TAO- patients were found to be positive for ANA and 3/24 TAO+ and 4/26 TAO- patients showed anti-SM antibodies. Conversely, when compared with HD control sera, GD sera showed antibodies to all individual ECM molecules. Remarkably, anti-CHI autoantibodies of the IgG isotype were significantly associated with GD TAO+ patients (p=0.045). Indeed, 6 out of 24 GD TAO+ patients scored positive for anti-CIII IgGs as compared to only 1 out of 26 TAO-. Our results suggest the potential involvement of anti-ECM antibodies in GD and a contribution of anti-CIII IgGs in TAO pathogenesis of GD patients.

Visual experience during early postnatal life is essential for normal development of synaptic connections in the visual system. In fact, altered visual experiences such as monocular deprivation (MD) or abnormal visual stimulation (e.g. strabismus, anisometropia) during this period disrupt the physiologic organization of the visual pathway, leading to loss of visual responses in cortical neurons and reduction in visual acuity of the affected eye, so that it becomes amblyopic. The authors review the main functional and morphologic changes induced by altered visual experiences in the developing visual system and focus on the recent discovery that MD induces apoptotic cell death in the lateral geniculate nucleus of newborn rats. Particular attention is given to the authors' studies documenting that, during development, MD leads retinal terminals to release excessive glutamate in the lateral geniculate nucleus where it elevates nitric oxide and causes DNA fragmentation. The latter event is known to activate poly-(ADP-ribose) polymerase, which in turn may trigger apoptosis. Better understanding of the mechanisms underlying the morphologic changes induced by altered visual experiences during development may open new venues for studying novel neuroprotective strategies for amblyopia and, more generally, for the treatment of ophthalmic diseases associated with neuronal apoptosis.

There are many different strategies for the treatment of the main bile duct lithiasis. When lithiasis of the biliary tract is suspected at a preoperative stage, we can treat patients with sequential treatment: endoscopic netrograde cholangiopancreatography followed by laparoscopic cholecystectomy. If common bile ductlithiasis is recognized at an intraoperative stage, many options for treatment exist, one of which is intraoperative retrograde endoscopic sphincterotomy (ES) (laparoendorendezvous). We report our experience using the aforementioned technique with 58 patients affected by cholelithiasis and complex Common bile duct disease who underwent laparoscopic cholecystectomy and intraoperative ES consecutively from March 1996 to May 2000. Of the 58 patients, 43 were affected by cholecystocholedocolithiasis: 12 by previously described lithiasis plus stenosant papillitis, 2 also by a pancreas head cancer, and 1 by cancer of the papilla. The combined technique was performed in 86% of the cases. Six patients required conversion to open surgery. In two other patients, laparoscopic choledocotomy was performed with positioning of a Kehr-tube for an ampulla-impacted lithiasis. Intraoperative ES offers a valid approach to the treatment of cholecystocholedocolithiasis in one session. Furthermore, it represents a valid alternative to transcholedocical laparoscopic treatment of cholelithiasis and complex common bite duct pathology.

We applied cDNA selection methods to a genomic clone (YAC 761B5) from chromosome 21 located in the so‐called ‘Down critical region’ in 21q22.3. Starting from human fetal heart and brain mRNAs we obtained and sequenced several cDNA clones. One of these clones (Down region aspartic protease (DRAP), named also BACE2 according to the gene nomenclature) revealed a striking nucleotide and amino acid sequence identity with several motifs present in members of the aspartic protease family. In particular the amino acid sequences comprising the two catalytic sites found in all mammalian aspartic proteases are perfectly conserved. Interestingly, the predicted protein shows a typical membrane spanning region; this is at variance with most other known aspartic proteases, which are soluble molecules. We present preliminary evidence, on the basis of in vitro translation studies and cell transfection, that this gene encodes a glycosylated protein which localizes mainly intracellularly but to some extent also to the plasma membrane. Furthermore DRAP/BACE2 shares a high homology with a newly described β‐secretase enzyme (BACE‐1) which is a transmembrane aspartic protease. The implications of this finding for Down syndrome are discussed.

The paper discusses basic principles and validity limits of the field-to-transmission line coupling calculation using Transmission Line (TL) theory. Particular attention is given to the EMP-power lines interaction. A detailed review of the fundamental equations and method of solution is given, considering that two equivalent formulations are possible. These result in two equivalent circuits for an elementary section of the transmission line, each characterized by different excitation source terms. The excitation sources for the case of a nuclear EMP excitation are modeled, and the solution of the equations is given taking into account the effect of a lossy earth serving as a return conductor. In order to assess the validity limits of the TL approximation, a comparison is made between results obtained by the authors using this approach, with those published in the literature using the scattering theory. The effect of shield overhead wires on the response of a power transmission line to an EMP is also investigated. It is shown that overhead shield wires, placed in the vicinity of the phase conductors for the purpose of providing protection of the system from lightning surges, can be considered effective also when the power line is illuminated by an incident electromagnetic pulse.

EXPOSURE of adult rabbits to darkness for 48 h produces bilateral DNA fragmentation in the lateral geniculate nucleus as revealed in brain sections by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) technique, suggesting an apoptotic type of cell death. In agreement with the latter deduction, light microscopy assessment of the morphological characteristics showed marginalization and condensation of nuclear chromatin, typical features of apoptosis. These effects were abolished by systemic administration of Nω-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthesis, whereas the D isomer was ineffective. In conclusion, the present data demonstrate that light deprivation for 48 h produces apoptosis in the lateral geniculate nucleus of rabbit and suggest that NO might be involved.

Clinical data and the common embryological origin of the pigment epithelium of the iris and retinal pigment epithelium suggest that the latter may be involved in the pigment dispersion syndrome (PDS). In our study functional changes of the retinal pigment epithelium were evaluated by electro-oculography in 10 PDS patients, 10 patients with chronic open-angle glaucoma (COAG) and 10 normal subjects. The mean dark-trough latency and Arden ratio for the PDS group were significantly lower than those of the COAG and control groups. Analysis of the Arden ratios based on the Kruskall-Wallis test revealed that 30% of the PDS values were subnormal with respect to the control group mean –1 SD. These results indicate primary involvement of the retinal pigment epithelium in PDS.

Background The protozoan disease giardiasis can cause ocular complications, including "salt and pepper" retinal changes. Methods Ophthalmic examinations were performed in 141 children (mean age 4.7 (SD 2.0) years) with active or past giardiasis diagnosed on the basis of microscopic examination of stool specimens or duodenal secretions--53 were newly diagnosed and untreated (group A), 50 had active infections in spite of metronidazole therapy (group B), and 38 had been successfully treated, with negative stool specimens for 1-3 years (group C). 300 children with no evidence of giardiasis were used as controls. Results Salt and pepper retinal changes (with normal electroretinographic findings) were diagnosed in 28 (19.9%) of the patients with giardiasis (11 from group A, 10 from group B, and seven from group C), including five pairs of siblings. In all subgroups, the children with retinal changes were consistently younger than those with normal retinas. In eight cases, the lesions could be visualised only with direct ophthalmoscopy. Conclusion Our findings indicate that asymptomatic, non-progressive retinal lesions are particularly common in younger children with giardiasis. This risk does not seem to be related to the severity of the infection, its duration, or the use of metronidazole but may reflect a genetic predisposition.

In this paper, simultaneous GPS time‐stamped measurements of the electric and magnetic fields at three distances and of the return stroke current associated with lightning strikes to the Toronto CN Tower (553 m) during the summer of 2005 are presented. The lightning return stroke current was measured using a Rogowski coil installed at a height of 474 m above ground level (AGL). The vertical component of the electric field and the azimuthal component of the magnetic field were measured simultaneously at distances of 2.0 km, 16.8 km, and 50.9 km from the CN Tower. The propagation path from the CN Tower to the first two stations (2.0 and 16.8 km) was along the soil and through the Toronto city, whereas for the third location (50.9 km) the propagation path was nearly entirely across Lake Ontario. The waveforms of the electric and magnetic fields at 16.8 km and 50.9 km exhibit a first zero crossing about 5 μs after the onset of the return stroke. This early zero crossing is part of a narrow undershoot. For fields at 50.9 km the expected zero crossing at about 40 μs is also observed. Metallic beams and other conducting parts in buildings on which electric and magnetic field sensors were located cause an enhancement effect on the measured fields. Although an enhancement can be identified both on the electric and the magnetic fields, the degree of enhancement is actually more significant for the electric field than for the magnetic field. It is shown that the value of the wave impedance (E‐field peak to H‐field peak ratio) could give an estimate of the enhancement effect of the building on the electric field. Propagation effects (decrease of field amplitude and increase of its risetime) can also be observed in experimental records. It is shown that the fields at 50.9 km are less affected by such attenuation, compared to those at 16.8 km, presumably because the path of propagation is mostly across Lake Ontario. Measured waveforms are compared with theoretical predictions obtained using the five engineering return stroke models extended to include the presence of the strike object, namely, transmission line (TL), modified transmission line (MTLL and MTLE), Bruce‐Golde (BG), and traveling current source (TCS) models. A reasonable agreement is found with all five engineering models for the magnetic field waveforms at the three considered distances, although the peak values of the computed fields are systematically about 25% lower than measured values. None of the models was able to reproduce the early zero crossing and the narrow undershoot. As far as the electric field is concerned, larger differences have been observed between simulations and measurements. This may be due to the fact that the enhancement effect of the building on the electric field is stronger than that on the magnetic field. The expression relating current and field peaks associated with strikes to tall structures is also tested versus obtained sets of experimental data. The overall agreement between the theoretically predicted and the experimentally observed field‐to‐current ratio is reasonable, although the formula of Bermudez et al. (2005) appears also to underestimate the experimentally measured ratio (by about 25%). This may be due, at least in part, to the enhancement effect of the buildings on which the field measurement antennae were installed.

In this paper, analytical expressions relating far fields and currents associated with lightning strikes to tall towers are derived. The derived equations are general and can be used with any engineering model. It is shown that the far field can be decomposed into three terms, namely (1) contribution of the main return stroke pulse along the lightning channel, (2) contribution of the multiple‐reflection process along the elevated strike object, including the contribution of upward propagating pulses transmitted into the channel, and (3) contribution of the so‐called “turn‐on” terms, associated with the current discontinuity at the return stroke wavefront. This discontinuity is associated with neglecting reflections at the upward moving front. It is also shown that only the first term is model‐dependent and that the far field–current relationship does not significantly depend on the adopted engineering model. It is therefore possible to use the analytical equation relating the current peak and the associated distant electric or magnetic fields, derived by Bermudez et al. (2005) for the transmission line (TL) model, for any engineering model extended to include a tall strike object. It is also shown that the peak amplitude of the electromagnetic field radiated by a lightning strike to a tall structure is relatively insensitive both to the value of the return stroke speed and the top reflection coefficient. These results and findings of this paper emphasize the key differences between return strokes initiated at ground level (or from short strike objects) and those striking tall towers: (1) The electromagnetic field from lightning strikes to tall towers is largely determined by the tower and only to a lesser extent by the channel, (2) electromagnetic fields associated with tall strike objects are less model‐sensitive than those corresponding to a strike to ground; in particular, the early time response of the field is nearly model‐independent, and (3) unlike ground‐initiated strikes, for which the far field peak is strongly dependent on the return stroke speed (proportional according to the TL model), far field peaks associated with strikes to tall strike objects are little sensitive to the return stroke speed. This is a particularly interesting result when lightning currents are measured directly on instrumented towers to calibrate the performance of lightning location systems, since in most practical cases the value of the return stroke speed is unknown. Note that points (2) and (3) can be considered as corollaries of point (1).