Assessment of Visual Function and Retinal Structure Following Acute Light Exposure in the Light Sensitive T4R Rhodopsin Mutant Dog

The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4–5.5 months) were used in this study: 3 homozygous mutant RHOT4R/T4R, 8 heterozygous mutant RHOT4R/+, and 3 normal wild-type (WT) dogs. Following overnight dark adaptation, the left eyes were acutely exposed to bright white light with a monocular Ganzfeld dome, while the contralateral right eye was shielded. Each of the 3 homozygous (RHOT4R/T4R) mutant dogs had a single unilateral light exposure (LE) to a different (low, moderate, and high) dose of white light (corneal irradiance/illuminance: 0.1 mW/cm2 , 170 lux; 0.5 mW/cm2 , 820 lux; or 1 mW/cm2 , 1590 lux) for 1min. All 8 heterozygous (RHOT4R/+) mutant dogs were exposed once to the same moderate dose of light. The 3 WT dogs had their left eyes exposed 1, 2, or 3 times to the same highest dose of light. Visual function prior to LE and at 2 weeks and 33 weeks after exposure was objectively assessed in the RHOT4R/T4R and WT dogs by using an obstacle-avoidance course. Transit time through the obstacle course was measured under different scotopic to photopic ambient illuminations. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging and histology before and at several time-points (2–36 weeks) after light exposure. The analysis of the transit time through the obstacle course showed that no differences were observed in any of mutant or WT dogs at 2 weeks and 33 weeks post LE. The RHOT4R/T4R retina exposed to the lowest dose of white light showed no obvious changes in ONL thickness at 2 weeks, but mild decrease was noted 36 weeks after LE. The RHOT4R/T4R retina that received a moderate dose (showed an obvious decrease in ONL thickness along the superior and temporal meridians at 2 weeks post LE with more severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/ tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors

Analysis of a semi-stationary cyclone on the coast of southern Brazil associated to an atmospheric blocking

Na primeira semana de maio de 2008, durante quatro dias, um ciclone em superfície permaneceu semi-estacionário na costa da região sul do Brasil. Este sistema foi responsável por chuvas e ventos fortes no Rio Grande do Sul e Santa Catarina, os quais causaram muitos danos (queda de árvores, enchentes e desabamentos). O objetivo deste trabalho é avaliar o processo de formação e entender os mecanismos responsáveis pelo lento deslocamento do ciclone, já que a maioria dos ciclones nesta região possui deslocamento mais rápido. A equação de desenvolvimento de Sutcliffe mostrou que a advecção de vorticidade absoluta ciclônica na média troposfera e a advecção de ar quente na camada entre 1000-500 hPa foram mecanismos importantes para a ciclogênese. Neste período, o intenso aquecimento diabático também contribuiu para a ciclogênese, à medida que se contrapôs ao intenso resfriamento adiabático devido aos movimentos verticais ascendentes. A advecção de vorticidade absoluta ciclônica que favoreceu a ciclogênese esteve associada a um Vórtice Ciclônico em Altos Níveis (VCAN), que se formou numa região de anomalia de vorticidade potencial. O VCAN se manteve semi-estacionário e compôs o setor norte de um bloqueio do tipo dipolo. Tal bloqueio intensificou um anticiclone em superfície, situado a sul/leste do ciclone, o que contribuiu para o ciclone se manter semi-estacionário. O movimento atípico e lento do ciclone para sul, e em alguns períodos para sudoeste, esteve associado com advecções de vorticidade absoluta ciclônica na média troposfera e de ar quente no seu setor sul. Somente quando o bloqueio em níveis médios e a anomalia de vorticidade potencial em níveis médios/altos se enfraqueceram, o ciclone em superfície se afastou da costa sul do Brasil.On the first week of May 2008, during four days, a semi-stationary surface cyclone acted over the coast of southern Brazil. This system was responsible for large amount of rain and strong near surface winds over Rio Grande do Sul and Santa Catarina causing many damages (fallen trees, floodings and landslides). This work evaluated cyclone development process to understand the reasons for its slow displacement, once most cyclones developed in this region move faster. The Sutcliffe development equation showed that cyclonic absolute vorticity advection in middle troposphere, and positive thermal advection in layer between 1000-500 hPa were important mechanisms for cyclogenesis processes. In this same period, diabatic heating also contributes to cyclogenesis as far as it was opposite to adiabatic cooling due to strong upward movement. Cyclonic absolute vorticity advection which propitiated cyclogenesis was associated with an Upper Level Cyclonic Vortex (ULCV) developed in a potential vorticity anomaly region. The ULCV was semi-stationary and part of a blocking dipole pattern. This blocking intensified a surface anticyclone at south/east of the cyclone, contributing to the cyclone staying semi-stationary near the coast of southern Brazil. The slow and unusual surface cyclone movement to south and sometimes to southwest was associated with middle level cyclonic absolute vorticity and warm air advections in their southern sector. Only when middle levels blocking and middle/high levels potential vorticity anomaly weakened, surface cyclone moved away from the coast of Southern Brazil.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Distrofia Miotônica Tipo 1: Frequência Dos Achados Oftalmológicos

The purpose of the study was to evaluate the frequency of ophthalmologic abnormalities in a cohort of myotonic dystrophy type 1 (DM1) patients and to correlate them with motor function. We reviewed the pathophysiology of cataract and low intraocular pressure (IOP). Method: Patients were included after clinical and laboratory diagnosis and after signed informed consent. They were evaluated by Motor Function Measure scale, Portuguese version (MFM-P) and ophthalmic protocol. Results: We evaluated 42 patients aged 17 to 64 years (mean 40.7 ± 12.5), 22 of which were men. IOP (n = 41) was reduced in all but one. We found cataract or positivity for surgery in 38 (90.48%) and ptosis in 23 (54.76%). These signs but not IOP were significantly correlated with severity of motor dysfunction. Abnormalities in ocular motility and stereopsis were observed. Conclusion: Cataract and ptosis are frequent in DM1 and associated to motor dysfunction. Reduced IOP is also common, but appears not to be related with motor impairment. © 2016, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.74318318

Comparative study of muscular tonus in spastic tetraparetic cerebral palsy in children with predominantly cortical and subcortical lesions in computerized tomography of the skull

OBJECTIVE: To compare distribution and intensity of muscular tonus in spastic tetraparetic cerebral palsy (CP), correlating the clinical data with lesion location in the central nervous system. METHOD: Twelve children aged two to four years old with predominantly cortical lesions (six children) and subcortical lesions (six children) were included. The tonus was analyzed in the upper (UULL) and lower limbs (LLLL) based on Durigon and Piemonte protocol. RESULT: There was no significant difference regarding tonus intensity and distribution in the UULL and LLLL in both groups. Comparing the upper and lower limbs of subjects in the same group, the LLLL presented more asymmetry and higher tonus intensity than the UULL. CONCLUSION: In this study children with CP as a result of predominantly cortical or subcortical lesions present a similar deficit in tonus modulation, causing a symmetric and homogeneous distribution of hypertonicity, which is predominant in the LLLL.OBJETIVO: Comparar a distribuição e intensidade do tono muscular na paralisia cerebral tetraparética espástica (PC-T), correlacionando os dados clínicos com a localização da lesão no sistema nervoso central. MÉTODO: Foram incluídas 12 crianças de dois a quatro anos de idade com lesões predominantemente corticais (seis crianças) e subcorticais (seis crianças). O tono foi analisado nos membros superiores (MMSS) e inferiores (MMII) baseado no protocolo de Durigon e Piemonte. RESULTADOS: Não houve diferença significante quanto à intensidade e distribuição de tono em MMSS e MMII nos dois grupos. Comparando os MMSS e MMII de sujeitos do mesmo grupo, os MMII apresentaram mais assimetrias e maior intensidade do tono do que os MMSS. CONCLUSÃO: Neste estudo, crianças com PC devido a lesões predominantemente corticais ou subcorticais apresentam déficit semelhante na modulação de tono, ocasionando distribuição simétrica e homogênea de hipertonia que predomina em MMII.61762

Using virtual reality for motor rehabilitation in a child with ataxic cerebral palsy: case report

Was evaluated the influence of Virtual Reality (VR) with Nintendo Wii (NW) on balance and gait of a children with ataxic cerebral palsy (CP-A). A case study, child male, 12 years, diagnosis of CP-A without history of respiratory, cardiac or orthopedic previous diseases, independent and preserved cognitive march, attended the premises of Amarati entity located in Jundiaí (SP). Initially the child was assessed by the Scale Berg, Kay Cerny Protocol and GMFM-66. After it started the rehabilitation using VR, 3 times a week in 30 minute sessions, through games of NW(r), with the game Wii Fit Plus, Balance Board Wii Remote platform and control during 04 months, totaling 40 sessions. The child continued kinesiotherapeutic treatment within the institution during the collection period. With the end of the proposed period, the same parameters were reassessed. There was an increase in the GMFM-66 score with increasing average scores of 71.69 (SD 1.64) to 77.46 (SD 2.06) in the evolving dimensions "standing" and "walking, running and skip "; increase in scale Berg (from 48 to 53 points), indicating an improvement in static equilibrium; the protocol Kay Cerny shows no changes in the evaluated parameters (speed, frequency of steps/min, and last stride length and step width) were observed. These results suggest that the use of the NW influences the improvement mainly to balance the child when used in addition to the kinesiotherapeutic treatment, however is necessary to perform studies with larger populations for evidence of its effectiveness.Avaliou-se a influência da Realidade Virtual (RV) com Nintendo Wii (NW) no equilíbrio e na marcha de uma criança com Paralisia Cerebral Atáxica (PC-A). O trabalho é um estudo de caso com uma criança do gênero masculino, 12 anos, diagnosticada com PC-A, sem antecedentes de doenças respiratórias, cardíacas ou ortopédicas prévias, marcha independente e cognitivo preservado, atendida nas dependências da entidade Amarati, localizada em Jundiaí (SP). Inicialmente a criança foi avaliada pela escala de Berg, Protocolo de Kay Cerny, e GMFM-66. Depois se iniciou a reabilitação utilizando a RV 3 vezes por semana em sessões de até 30 minutos, através dos jogos do NW(r), com o jogo Wii Fit plus, plataforma Balance Board e controle Wii Remote durante 04 meses, totalizando 40 sessões. A criança continuou o tratamento cinesioterapêutico na própria instituição durante o período de coleta. Com o término do período proposto, os mesmos parâmetros foram reavaliados. Observou-se aumento na pontuação da GMFM-66 com aumento do escore médio de 71,69 (SD 1,64) para 77,46 (SD 2,06), evoluindo nas dimensões "em pé" e "andar, correr e pular"; aumento na escala de Berg (de 48 para 53 pontos), indicando melhora no equilíbrio estático; não foram observadas mudanças no protocolo de Kay Cerny nos parâmetros avaliados (velocidade, frequência de passos/min, comprimento do passo e passada e largura do passo). Os resultados apresentados sugerem que o uso do NW influencia na melhora principalmente do equilíbrio da criança quando usada em complemento com o tratamento cinesioterapêutico, porém é necessária a realização de estudos com populações maiores para comprovação de sua eficácia.Se ha evaluado la influencia de la Realidad Virtual (RV) con Nintendo WII (NW) para el equilibrio y la marcha de un niño con Parálisis Cerebral Ataxia (PC-A). Este trabajo es un estudio de caso con niño de 12 años de edad, diagnosticado con PC-A, sin antecedentes de enfermedades respiratorias, cardíacas u ortopédicas previas, marcha independiente y cognitivo preservado, que era asistido en las dependencias de una entidad Amarati, ubicada en Jundiaí (SP), Brasil. Al inicio, se evaluó el niño por la Escala de Berg, por el Protocolo de Kay Cerny, y por GMFM-66. Enseguida, tuvo inicio la rehabilitación con el uso de la RV 3 veces por semana en sesiones hasta 30 minutos de duración, a través de los juegos del NW(r), con el juego Wii Fit plus, plataforma Balance Board y control Wii Remote durante 04 meses, con un total de 40 sesiones. El niño siguió el tratamiento con kinesioterapia en la propia institución durante el periodo de la recolección. Con el término del periodo propuesto, los mismos parámetros se han reevaluados. Se observó el aumento en la puntuación de la GMFM-66 con una subida de la puntuación media de 71,69 (SD 1,64) para 77,46 (SD 2,06), la evolución en las dimensiones "de pie" y "andar, correr y saltar"; el aumento en la Escala de Berg (de 48 para 53 puntos), lo que indica una mejora en el equilibrio estático; no se han observado cambios en el protocolo de Kay Cerny en los parámetros evaluados (velocidad, frecuencia de pasos/min, extensión del paso y de la pasada y anchura del paso). Los resultados presentados muestran que el uso del NW hace una influencia en la mejora, en especial, del equilibrio del niño cuando se usa en complementación al tratamiento con kinesioterapia, pero es necesaria la realización de estudios con poblaciones mayores para comprobar su eficacia

Variabilities in Retinal Function and Structure in a Canine Model of Cone-Rod Dystrophy Associated With RPGRIP1 Support Multigenic Etiology

Defects in the cilia gene RPGRIP1 cause Leber congenital amaurosis and cone-rod dystrophy in humans. A form of canine cone-rod dystrophy (cord1) was originally associated with a homozygous insertion in RPGRIP1 (RPGRIP1ins/ins) as the primary disease locus while a homozygous deletion in MAP9(MAP9del/del) was later identified as a modifier associated with the early onset form. However, we find further variability in cone electroretinograms (ERGs) ranging from normal to absent in an extended RPGRIP1ins/ins canine colony, irrespective of the MAP9 genotype. Ophthalmoscopically, cone ERGabsentRPGRIP1ins/ins eyes show discolouration of the tapetal fundus with varying onset and disease progression, while sd-OCT reveals atrophic changes. Despite marked changes in cone ERG and retinal morphology, photopic vision-guided behaviour is comparable between normal and cone ERGabsentRPGRIP1ins/ins littermates. Cone morphology of the dogs lacking cone ERG are truncated with shortened outer and inner segments. Immunohistochemically, cone ERGabsentRPGRIP1ins/ins retinas have extensive L/M-opsin mislocalization, lack CNGB3 labelling in the L/M-cones, and lack GC1 in all cones. Our results indicate that cord1 is a multigenic disease in which mutations in neither RPGRIP1 nor MAP9 alone lead to visual deficits, and additional gene(s) contribute to cone-specific functional and morphologic defects

Acute bout of exercise downregulates thioredoxin-interacting protein expression in rat contracting skeletal muscles

We previously reported that in rat skeletal muscle, disuse (i.e., decreased muscle contractile activity) rapidly increases thioredoxin-interacting protein (TXNIP), which is implicated in the reduced glucose uptake. Accordingly, we sought herein to (a) determine the effect of exercise (i.e., increased muscle contractile activity) on muscle TXNIP protein expression, and (b) elucidate the mechanisms underlying the changes of TXNIP protein expression in response to exercise. Rat epitrochlearis and soleus muscles were dissected out after an acute bout of 3-hr swimming (without weight loading) or 3-hr treadmill running (15% grade at 9m/min). In a separate protocol, the isolated epitrochlearis and soleus muscles were incubated for 3 hr with AMP-dependent protein kinase activator AICAR. Immediately after the cessation of the 3-hr swimming, the TXNIP protein was decreased in epitrochlearis but not in soleus muscle. Conversely, 3-hr treadmill running decreased the TXNIP protein in soleus but not in epitrochlearis muscle. TXNIP protein was decreased concomitantly with reduced postexercise muscle glycogen, showing that a decrease in TXNIP protein expression occurs in muscles that are recruited during exercise. In addition, 3-hr incubation with AICAR decreased TXNIP protein in both isolated epitrochlearis and soleus muscles. Our results suggest that (a) an acute bout of exercise downregulates TXNIP protein expression in rat contracting skeletal muscles, and (b) the reduction in TXNIP protein expression in contracting muscles is probably mediated by AMPK activation, at least in part