Photoreceptor damage induced by low-intensity light: model of retinal degeneration in mammals

Purpose: Retinal degeneration caused by a defect in the phototransduction cascade leads to the apoptosis of photoreceptor cells, although the precise molecular mechanism is still unknown. In addition, constant low light exposure produces photoreceptor cell death through the activation of downstream phototransduction. The authors investigated the time course and molecular mechanisms of death and the rhodopsin phosphorylation occurring during retinal degeneration after exposure to continuous low-intensity light. Methods: Wistar rats were exposed to constant cool white 200 lx intensity LED light (LL) for one to ten days and compared with animals kept in the dark (DD) or controls exposed to a regular 12:12 h (LD) cycle. One eye from each rat was used for histological and quantitative outer nuclear layer (ONL) analysis and the other for biochemical assays. Results: The histological analysis showed a significant reduction in the ONL of LL-exposed rats after seven days compared with LD- or DD-exposed rats. Retinal analysis by flow cytometer and the TUNEL assay revealed an increase in cell death in the ONL, the in vitro enzymatic activity assay and western blot analysis showing no caspase-3 activation. The rhodopsin analysis demonstrated more phosphorylation in serine 334 residues (Ser334) in LL-exposed than in LD- or DD-exposed rats. However, for all times studied, rhodopsin was completely dephosphorylated after four days of DD treatment. Conclusions: Constant light exposure for seven days produces ONL reduction by photoreceptor cell death through a capase-3-independent mechanism. Increases in rhodopsin-phospho-Ser334 levels were observed, supporting the notion that changes in the regulation of the phototransduction cascade occur during retinal degeneration.Fil: Contin, Maria Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Arrieti, Milagros M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Benedetto, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Bussi, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba; Argentin

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study

To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. Methods: 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6 ± 9.8 y.o, disease duration 22 ± 35 months) underwent a 29-channel resting-state electroencephalography (EEG – 5 min opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs – N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7 ± 15.1 y.o). Results: Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers’ clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. Conclusions: We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. Significance: This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach

Using post-flood surveys and geomorphologic mapping to evaluate hydrological and hydraulic models: The flash flood of the Girona River (Spain) in 2007

This paper analyzes the Girona River (Spain) flash flood, occurred on the 12th of October 2007, combining hydrological and hydraulic modeling with geomorphologic mapping and post-flood survey information. This research aims to reproduce the flood event in order to understand and decipher the flood processes and dynamics on a system of prograding alluvial fans. The hydrological model TETIS was used to characterize the shape and dimension of the October 2007 Girona River hydrograph. Subsequently, the flood event was reproduced using the free surface flow module of the model RiverFlow2D. The combination of hydrological and hydraulic models was evaluated using post-flood surveys defining maximum flooded area and flood depths. Then, simulations with different peak discharges were carried out to estimate the hydro-geomorphologic response of the Girona River floodplain, through the identification of the activation thresholds in different geomorphic elements. Results showed that the unit peak discharge of the October 2007 flood event (5 m3 s−1 km−2) was among the largest ever recorded in the area, according to the existing literature. Likewise, the hydraulic model showed a good performance in reproducing the flood event (FitA = 76%, RMSE = 0.65 m and NSE = 0.6), despite the complexity of the case, an ephemeral and ungauged river. The model simulation revealed the existence of an activation pattern of paleochannels and alluvial fans, which was altered by the presence of some anthropogenic disturbances. This multidisciplinary approach proved to be a useful strategy for understanding flash flood processes in ungauged catchments. It allowed understanding the mechanisms governing floods in alluvial fans systems and it represented a solid contribution for early warning plans and risk mitigation policies.This collaborative research was financed with the projects CGL2013-44917-R and SLWAMED CGL2014-58127-C3-2, of the Ministry of Economy and Competitiveness of the Spanish Government. Both projects were co-financed with FEDER funds. The observed rainfall and water discharge records were provided by "Sistema Automatic de Information Hidrologica (SAIH)", which belongs to the CHJ (Spain). This work was also possible due to the kind cooperation of the members of the Plataforma Ciutadana Riu Girona and several anonymous farmers interviewed during the field works. We also thank two anonymous reviewers for their useful and thought-provoking comments.Segura-Beltrán, F.; Sanchis Ibor, C.; Morales-Hernández, M.; González-Sanchis, MDC.; Bussi, G.; Ortiz, E. (2016). Using post-flood surveys and geomorphologic mapping to evaluate hydrological and hydraulic models: The flash flood of the Girona River (Spain) in 2007. Journal of Hydrology. 541(Part A):310-329. https://doi.org/10.1016/j.jhydrol.2016.04.039S310329541Part

Obstructive sleep apnea in Prader-Willi syndrome: risks and advantages of adenotonsillectomy

Obstructive sleep apnea is a well-known clinical manifestation of Prader-Willi syndrome. The aim of our study is to evaluate the efficacy of adenotonsillectomy for the treatment of the disorder as well as the improvement of their post-operative quality of life. Five patients with moderate to severe obstructive sleep apneas and adenotonsillar hypertrophy of grade III-IV underwent adenotonsillectomy. Pre- and postoperative apneas and Quality of Life were assessed respectively with a polysomnography with multi-sleep latency test and with the pediatric Quality of Life questionnaire, performed before and 6 months after surgery. A decrease of apnea/hypopnea index values has been detected between pre- and post-surgery (t=2.64, P=0.005), as well as oxygen desaturation index values (t=5.51, P=0.005), multi-sleep latency test (t=4.54, P=0.01), and of the values of pediatric Quality of Life questionnaire. No correlation has been detected between body mass index and apnea/hypopnea index, oxygen desaturation index and multi-sleep latency test values pre- and post-adenotonsillectomy. A correlation has been found between multi-sleep latency test and oxygen desaturation index values post-surgery (P=0.04). No post-operative complications were observed. Our data underline the efficacy of surgery in Prader-Willi patients with adenotonsillar hypertrophy in order to improve their quality of life

Corrigendum: Clinical Features of Headache in Patients With Diagnosis of Definite Vestibular Migraine: The VM-Phenotypes Projects

[This corrects the article DOI: 10.3389/fneur.2018.00395.]

COVID-19 in the tonsillectomised population

Objective: Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. Methods: Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. Results: Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. Conclusions: A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models

Effects of lipid composition on membrane permeation

© 2018 The Royal Society of Chemistry. Passive permeation through lipid membranes is an essential process in biology. In vivo membranes typically consist of mixtures of lamellar and nonlamellar lipids. Lamellar lipids are characterized by their tendency to form lamellar sheet-like structures, which are predominant in nature. Nonlamellar lipids, when isolated, instead form more geometrically complex nonlamellar phases. While mixed lamellar/nonlamellar lipid membranes tend to adopt the ubiquitous lamellar bilayer structure, the presence of nonlamellar lipids is known to have profound effects on key membrane properties, such as internal distributions of stress and elastic properties, which in turn may alter related biological processes. This work focuses on one such process, i.e., permeation, by utilising atomistic molecular dynamics simulations in order to obtain transfer free energy profiles, diffusion profiles and permeation coefficients for a series of thirteen small molecules and drugs. Each permeant is tested on two bilayer membranes of different lipid composition, i.e., purely lamellar and mixed lamellar/nonlamellar. Our results indicate that the presence of nonlamellar lipids reduces permeation for smaller molecules (molecular weight 100). This work represents an advancement towards the development of more realistic in silico permeability assays, which may have a substantial future impact in the area of rational drug design