Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

Obesity during pregnancy on vagal tone, hemoglobin A1c, oxygenation, and perinatal outcomes

Purpose: To examine the effect of obesity and gestational weight gain on heart rate variability (HRV), oxygenation (HbO 2 and SpO2), hemoglobin A1c (HbA1c) and the frequency of pregnancy complications in obese (O) and non-obese (NO) women.^ Design: The study was an observational comparison study with a repeated measures design. ^ Setting: The setting was a low risk prenatal, university clinic located in a large southeastern metropolitan city. ^ Sample: The sample consisted of a volunteer group of 41 pregnant women who were observed at the three time points of 20, 28, and 36 weeks gestation. ^ Analysis: Analysis included general linear modeling with repeated measures to test for group differences with changes over time on vagal response, HbA1c, and oxygenation. Odds ratios were computed to compare the frequency of birth outcomes. ^ Findings: The interaction effect of time between O and NO women on HbO2 was significant. The mean HP, RSA, and HbO2 changed significantly over time within the NO women. The mean HbA 1c increased significantly over time within the O women. Women with excess gestational weight gain had significantly lower heart period than women with weight gain within the IOM recommendations. Obese women were more likely to have Group B streptococcal infections, gestational hypertension, give birth by cesarean or instrument assistance, and have at least one postnatal event. ^ Conclusions: Monitoring HRV, oxygenation, and HbA1c using minimally invasive measures may permit early identification of alterations in autonomic response. Implementation of interventions to promote vagal tone may help to reduce risks for adverse perinatal outcomes related to obesity. Future studies should examine the effect of obesity on the vagal response and perinatal outcomes. ^

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

COMPREENSÃO DO FUNCIONAMENTO MENTAL EM PACIENTES COM ACIDENTE CEREBROVASCULAR: UMA CONTRIBUIÇÃO DA PSICOLOGIA DA SAÚDE

O acidente cerebrovascular é uma doença de grande incidência no Brasil e no mundo. As pessoas que sofreram este tipo de acometimento podem apresentar seqüelas variadas, como motoras, cognitivas, sensoriais, sociais, afetivo-emocionais e transtornos psiquiátricos, levando a graus variados de dependência. Sendo assim, um estudo psicológico se faz importante, pois estas pessoas sofrerão mudanças em suas rotinas e no seu mundo interno.O presente trabalho trata-se de uma pesquisa clínico qualitativa, e teve como objetivos investigar as repercussões psicológicas de pacientes adultos que sofreram acidente cerebrovascular; compreender o funcionamento mental, a deterioração neuropsicológica e a adaptação humana desses pacientes, através da Escala de Avaliação Global do Funcionamento, do Desenho da Figura Humana, e da Escala do Diagnóstico Adaptativo Operacionalizado; compreender o sofrimento psicológico em narrativas da entrevista psicológica dessas pessoas e investigar como os indivíduos contam sua própria história numa compreensão psicossomática e psicanalítica. Para isso, utilizou-se o referencial teórico da Psicanálise e as concepções de Neuropsicanálise e Psicossomática. Foram analisados os relatos de cinco pacientes em tratamento num centro de reabilitação. Observou-se que por tratar-se de uma lesão cerebral, as repercussões psicológicas de quem sofreu acidente cerebrovascular devem ser observadas do ponto de vista neuropsicológico e a dinâmica afetivo-emocional. Os dados do Eixo V do DSM-IV, Escala de Avaliação Global do Funcionamento, e da Escala do Diagnóstico Adaptativo Operacionalizado de Ryad Simon apresentaram forte correlação estatística, embora a última seja mais compreensiva do ponto de vista psicanalítico; todos os pacientes apresentaram Adaptação Ineficaz. Quanto ao Desenho da Figura Humana, questionou-se a fidedignidade deste tipo de técnica nessa população, uma vez que os dados de organicidade interferem bastante. A história construída foi um instrumento importante para investigar como o indivíduo que sofreu acidente cerebrovascular contou sua própria história, seus mecanismos de defesa e as fantasias inconscientes, surgindo nesses relatos histórias importantes de depressão. Os mecanismos de defesa predominante no funcionamento mental desses pacientes foram a repressão e a desvalorização, no funcionamento neurótico, e a onipotência no funcionamento psicótico.(AU)

Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid

Transgenic mice that overexpress mutant human amyloid precursor protein (APP) exhibit one hallmark of Alzheimer’s disease pathology, namely the extracellular deposition of amyloid plaques. Here, we describe significant deposition of amyloid β (Aβ) in the cerebral vasculature [cerebral amyloid angiopathy (CAA)] in aging APP23 mice that had striking similarities to that observed in human aging and Alzheimer’s disease. Amyloid deposition occurred preferentially in arterioles and capillaries and within individual vessels showed a wide heterogeneity (ranging from a thin ring of amyloid in the vessel wall to large plaque-like extrusions into the neuropil). CAA was associated with local neuron loss, synaptic abnormalities, microglial activation, and microhemorrhage. Although several factors may contribute to CAA in humans, the neuronal origin of transgenic APP, high levels of Aβ in cerebrospinal fluid, and regional localization of CAA in APP23 mice suggest transport and drainage pathways rather than local production or blood uptake of Aβ as a primary mechanism underlying cerebrovascular amyloid formation. APP23 mice on an App-null background developed a similar degree of both plaques and CAA, providing further evidence that a neuronal source of APP/Aβ is sufficient to induce cerebrovascular amyloid and associated neurodegeneration.

Dopamine tone regulates D1 receptor trafficking and delivery in striatal neurons in dopamine transporter-deficient mice

In vivo, G protein-coupled receptors (GPCR) for neurotransmitters undergo complex intracellular trafficking that contribute to regulate their abundance at the cell surface. Here, we report a previously undescribed alteration in the subcellular localization of D1 dopamine receptor (D1R) that occurs in vivo in striatal dopaminoceptive neurons in response to chronic and constitutive hyperdopaminergia. Indeed, in mice lacking the dopamine transporter, D1R is in abnormally low abundance at the plasma membrane of cell bodies and dendrites and is largely accumulated in rough endoplasmic reticulum and Golgi apparatus. Decrease of striatal extracellular dopamine concentration with 6-hydroxydopamine (6- OHDA) in heterozygous mice restores delivery of the receptor from the cytoplasm to the plasma membrane in cell bodies. These results demonstrate that, in vivo, in the central nervous system, the storage in cytoplasmic compartments involved in synthesis and the membrane delivery contribute to regulate GPCR availability and abundance at the surface of the neurons under control of the neurotransmitter tone. Such regulation may contribute to modulate receptivity of neurons to their endogenous ligands and related exogenous drugs.

The spatial and temporal representation of a tone on the guinea pig basilar membrane

In the mammalian cochlea, the basilar membrane's (BM) mechanical responses are amplified, and frequency tuning is sharpened through active feedback from the electromotile outer hair cells (OHCs). To be effective, OHC feedback must be delivered to the correct region of the BM and introduced at the appropriate time in each cycle of BM displacement. To investigate when OHCs contribute to cochlear amplification, a laser-diode interferometer was used to measure tone-evoked BM displacements in the basal turn of the guinea pig cochlea. Measurements were made at multiple sites across the width of the BM, which are tuned to the same characteristic frequency (CF). In response to CF tones, the largest displacements occur in the OHC region and phase lead those measured beneath the outer pillar cells and adjacent to the spiral ligament by about 90°. Postmortem, responses beneath the OHCs are reduced by up to 65 dB, and all regions across the width of the BM move in unison. We suggest that OHCs amplify BM responses to CF tones when the BM is moving at maximum velocity. In regions of the BM where OHCs contribute to its motion, the responses are compressive and nonlinear. We measured the distribution of nonlinear compressive vibrations along the length of the BM in response to a single frequency tone and estimated that OHC amplification is restricted to a 1.25- to 1.40-mm length of BM centered on the CF place.

Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression.

Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO2 inhalation. In mice with deletion of the gene for neuronal NO synthase (NOS), CO2 inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N omega-nitro-L-arginine, and CO2 exposure fails to increase brain levels of cGMP. Topical acetylcholine elicits vasodilation in the mutants which is blocked by N omega-nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO.

Season-Long Examination of the Intervention Tone of Coach-Athlete Interactions and Athlete Development in Youth Sport

Objectives: Coaches are a primary influence on athletes' development in youth sport (Horn, 2008). However, the intervention tone of coaches' behaviour has not been directly observed. The purpose of this study was to examine associations between the intervention tone exhibited by youth sport coaches and athletes' individual developmental trajectories over the course of a season. Design: Short-term longitudinal study with behavioural observation. Method: Fifty-five athletes and their coaches from five youth volleyball teams were observed at three time points, and the intervention tone of interactive behaviour was systematically coded and organized by coach-athlete dyad. Athletes completed measures of the 4C's of athlete development (competence, confidence, connection, character) at each time point, which were used to create individualized developmental trajectories. Person-centred analyses were used to examine associations between athletes' developmental trajectories and their unique interactive experiences with their coach. Results: Cluster analysis revealed the presence of three distinct clusters based on athletes' developmental trajectories: 1) high and increasing, 2) low and decreasing, and 3) moderate and maintaining, with athletes from each team distributed across clusters. Analysis of dyadic interaction profiles revealed significant differences in interactive behaviour between clusters. Conclusions: Results suggest that differences in coach-athlete interactive experiences are associated with different developmental trajectories over the course of a season, even for athletes working with the same coach, highlighting the individualized nature of coaches' influence on young athletes. Practical implications for coaches include a critical awareness of their unique interactive relationship with each athlete independently, as well as the importance of fostering these relationships with regard to young people as more than just athletes.

Posterior circulation cerebrovascular syndromes: diagnosis and management.

One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

Manners and tone of good society. Or, Solecisms to be avoided.

Mode of access: Internet.