Numerical simulation of the aqueous humor flow in the eye drainage system; a healthy and pathological condition comparison.

The present work describes the motion of aqueous humor through the anterior chamber and the trabecular drainage system, considering several distributions of the collector channels. The 3D computational model, implemented into the open-source software, was reconstructed from an optical coherence tomography. The model has been employed to simulate the aqueous humor dynamics considering buoyancy effects. The presence of the anterior chamber, the trabecular meshwork, and the Schlemm's canal were taken into consideration with 14 different distributions of collector channels. The influence of collector channels position on the intraocular pressure and shear stress has been analyzed, for a healthy and a glaucomatous condition. Aqueous humor velocity, pressure, temperature, wall shear stress, skin friction coefficient and Nusselt number, are presented for the different cases. The results indicate that the position of the collector channels has a strong influence on the wall shear stress on the Schlemm's canal and collector channels.

Frequency response curves for a Mooney-Rivlin hyperelastic microbubble oscillating as a contrast agent in an acoustic pressure field.

In this work, we have developed numerical simulations and weakly nonlinear analysis based on the multiple-scales perturbation technique for a coated microbubble that performs radial pulsations subject to an acoustic pressure disturbance in the far-field and whose encapsulated hyperelastic material obeys the Mooney-Rivlin equation. Departing from an elastic coating as a hyperelastic shell of finite thickness, we assume eventually that the shell is of very small thickness in comparison with the microbubble radius. Under this condition, we then perform weakly nonlinear analysis, to identify resonance conditions for small pressure disturbances of the acoustic field. In parallel and also for the limit of small thickness, we have carried out numerical simulations of the radial motion of the microbubble, identifying the onset of limit cycles via the construction of Poincare maps. Under both schemes, we have recognized the importance of two dimensionless hyperelastic parameters that dictate the main behavior of the oscillations: α∗ and ß∗. Decreasing the values of these parameters, the resonance conditions are drastically amplified, which is an expected result because of the weak rigidity of the hyperelastic solid, prevails. In this manner, we suggest that moderate values for these previous parameters can be widely advisable when, in medical diagnostic applications, we are applying microbubbles as contrast agents. Therefore, we recommend widely the use of shell softens, because in this case the amplitude of radial pulsation is always amplified.

Social interactions impact on the dopaminergic system and drive individuality.

Individuality is a striking feature of animal behavior. Individual animals differ in traits and preferences which shape their interactions and their prospects for survival. However, the mechanisms underlying behavioral individuation are poorly understood and are generally considered to be genetic-based. Here, we devised a large environment, Souris City, in which mice live continuously in large groups. We observed the emergence of individual differences in social behavior, activity levels, and cognitive traits, even though the animals had low genetic diversity (inbred C57BL/6J strain). We further show that the phenotypic divergence in individual behaviors was mirrored by developing differences in midbrain dopamine neuron firing properties. Strikingly, modifying the social environment resulted in a fast re-adaptation of both the animal's traits and its dopamine firing pattern. Individuality can rapidly change upon social challenges, and does not just depend on the genetic status or the accumulation of small differences throughout development.

Outcomes of ventriculoperitoneal shunt insertion in the management of idiopathic intracranial hypertension in children.

PURPOSE: The ventriculoperitoneal (VP) shunt has become the procedure of choice for treatment of idiopathic intracranial hypertension (IIH). We aimed to assess the efficacy of frameless stereotactic placement of VP shunts for the management of medically resistant IIH in children and to assess the role of gender and obesity in the aetiology of the condition. METHODS: This is a retrospective analysis of the case notes of 10 patients treated surgically at the University Hospital of Wales in Cardiff, from May 2006 to September 2012. RESULTS: VP shunts were successful in relieving headache, papilloedema and stabilising vision. No sex predilection was identified, and increased BMI was a feature throughout the population, regardless of age. CONCLUSIONS: Neuronavigated VP shunt insertion is an effective mode of treatment for medically resistant IIH in children. The aetiological picture in children does not seem to be dominated by obesity, as in adults. Literature on childhood IIH is sparse, and larger scale, comparative studies would be of benefit to treating clinicians.

Role of nicotinic acetylcholine receptors in regulating dopamine neuron activity.

Midbrain dopamine (DA) neurons play a central role in a wide range of behaviors, from attention and motivation to motor control and reinforcement. The release of DA is modulated by a number of factors, and its deregulation has been implicated in multiple psychiatric disorders, such as addiction. In particular, nicotinic acetylcholine receptors (nAChRs) are key modulators of DA cells. Nicotine, the main addictive component in tobacco, strongly interacts with these receptors in the midbrain DA systems, resulting in reinforcing effects that are at the core of tobacco addiction. nAChRs are virtually expressed on every cell of the DA system, both at pre-, post- and extra-synaptic locations. The complex issue of interpreting the role of the large portfolio of different nAChR subtypes expressed on ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) neurons, and especially their role in defining functional DAergic subpopulations, is far from being solved. In this review we will try to provide the reader with an integrative view of the nicotinic modulation of DA neurons and its influence at the cellular, systemic and behavioral levels (exploratory behavior), as well as its implication in the reinforcing effects of nicotine.

Vagal nerve stimulation in children under 12 years old with medically intractable epilepsy.

OBJECTIVE: This study aims to assess the efficacy and safety of vagal nerve stimulation (VNS) in children less than 12 years old operated on at the University Hospital Wales. METHOD: Retrospective review of patients undergoing VNS insertion, over a 3-year period, was undertaken. All children had a minimum follow-up period of 2 years. Sixteen patients were identified via the paediatric epilepsy surgery database. A case note review and telephone evaluation was conducted. Seizure frequency using the McHugh classification was the primary outcome measure, with anti-epileptic drug (AED) use as a secondary outcome measure. RESULTS: There were 10 males and 6 females. The mean time with epilepsy prior to surgery was 5.7 years and the mean age at the time of surgery was 7.6 years. Overall, nine (56 %) children experienced a reduction in their seizure frequency of 50 % or more. Of these, four (25 %) had a reduction of more than 80 %. Seven children (44 %) had no reduction in their seizure frequency, although two of these patients reported benefit regarding seizure control and post-ictal recovery. The VNS system was removed in two patients due to infection and no benefit, respectively. Half of the cohort (50 %) reduced the number of anti-epileptic drugs post-surgery, and there was an overall mean reduction of AED of 0.5. CONCLUSION: This study suggests that VNS is a safe and effective adjuvant therapy in children under 12 years old, with over half reporting significant benefit. Further studies are needed to enable preoperative selection of patients in order to maximise the potential benefit.

A theory of rate coding control by intrinsic plasticity effects.

Intrinsic plasticity (IP) is a ubiquitous activity-dependent process regulating neuronal excitability and a cellular correlate of behavioral learning and neuronal homeostasis. Because IP is induced rapidly and maintained long-term, it likely represents a major determinant of adaptive collective neuronal dynamics. However, assessing the exact impact of IP has remained elusive. Indeed, it is extremely difficult disentangling the complex non-linear interaction between IP effects, by which conductance changes alter neuronal activity, and IP rules, whereby activity modifies conductance via signaling pathways. Moreover, the two major IP effects on firing rate, threshold and gain modulation, remain unknown in their very mechanisms. Here, using extensive simulations and sensitivity analysis of Hodgkin-Huxley models, we show that threshold and gain modulation are accounted for by maximal conductance plasticity of conductance that situate in two separate domains of the parameter space corresponding to sub- and supra-threshold conductance (i.e. activating below or above the spike onset threshold potential). Analyzing equivalent integrate-and-fire models, we provide formal expressions of sensitivities relating to conductance parameters, unraveling unprecedented mechanisms governing IP effects. Our results generalize to the IP of other conductance parameters and allow strong inference for calcium-gated conductance, yielding a general picture that accounts for a large repertoire of experimental observations. The expressions we provide can be combined with IP rules in rate or spiking models, offering a general framework to systematically assess the computational consequences of IP of pharmacologically identified conductance with both fine grain description and mathematical tractability. We provide an example of such IP loop model addressing the important issue of the homeostatic regulation of spontaneous discharge. Because we do not formulate any assumptions on modification rules, the present theory is also relevant to other neural processes involving excitability changes, such as neuromodulation, development, aging and neural disorders.

The prevalence of neuromyelitis optica in South East Wales.

BACKGROUND AND PURPOSE: Neuromyeltis optica (NMO) is a neuroinflammatory disorder considered rare in Caucasian populations. However, accurate population-based epidemiological data for NMO and NMO spectrum disorder (NMO-SD) from Western populations employing validated diagnostic criteria remain limited. We sought therefore to estimate the prevalence and clinical features of NMO in a north European Caucasian population in South East Wales. METHODS: Patients were identified by a comprehensive, multistage ascertainment strategy employing a regional neuroinflammatory disease register, hospital diagnostic databases personal physician referrals and regional requests for anti-aquaporin-4 antibodies (anti-AQP4). RESULTS: Fourteen Caucasian patients (11 patients with NMO and three with NMO-SD) were identified in a population of 712,572 (19.6/million; 95% CIs: 12.2-29.7). There was an excess of females (female:male 12:2), 11/14 were anti-AQP4 positive and 5/14 had disease onset under the age of 20 years. CONCLUSION: This study suggests that NMO and related spectrum disorders are at least as frequent in Northern European populations as in non-Caucasian populations and that the demographic profile of prevalent patients differs from clinic-based cohorts.

Beta2-containing neuronal nicotinic receptors as major actors in the flexible choice between conflicting motivations.

Beside a critical role in nicotine addiction, the role of nicotinic receptors in cognitive or emotional processes remains difficult to elucidate, mostly because of a lack of specificity of compounds and because they up or down regulate easily. Using knockout mice may be one key to elucidate the role of nicotinic receptors stimulated by their endogenous ligand acetylcholine. We and others have previously explored the behaviour of mice knockout for the beta2-subunit containing nicotinic receptor - ß2*nAChRs - ß2(-/-) mice. These mice exhibit a particular kind of hyperactive locomotion, with profound deficits in cognitive and social interaction tasks, only when they have to show flexible choices. We wonder here whether the latter is due to a lack of motor control - i.e. motor impulsivity, a lack of estimation of reward value - i.e. cognitive impulsivity, and/or a lack of appropriate ranking or choice between different motivations. We designed behavioural tasks allowing the study of these distinct processes in mice. Our current results highlight the important role of ß2*nAChRs in flexible behaviours in conflicting situations, such as social contact, spatial exploration and food consumption. They also show that the cognitive deficits exhibited by ß2(-/-) mice cannot be explained by impaired inhibitory behaviours. Although social cognition is considerably enriched in humans as compared to rodents, we provide here novel data for the neurobiology of flexible social behaviours that could ultimately be useful for humans. Indeed, the ability to show flexible behaviours and to display adapted social interactions is profoundly impaired in a myriad of psychiatric disorders.

Lung function loss in relation to silica dust exposure in South African gold miners.

OBJECTIVE: To estimate exposure-response relationships between respirable dust, respirable quartz and lung function loss in black South African gold miners. METHODS: 520 mineworkers aged >37 years were enrolled in a cross-sectional study. Gravimetric dust measurements were used to calculate cumulative respirable dust and quartz exposures. Excess lung function loss was defined as predicted minus observed forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). The association between excess loss and exposure was estimated, adjusting for smoking, tuberculosis and silicosis. RESULTS: Mean service length was 21.8 years, mean respirable dust 0.37 mg/m(3) and mean respirable quartz 0.053 mg/m(3). After adjustment, 1 mg-yr/m(3) increase in cumulative respirable dust exposure was associated with 18.7 ml mean excess loss in FVC [95% confidence interval (CI) 0.3, 37.1] and 16.2 ml in FEV1 (95% CI -0.3, 32.6). Mean excess loss with silicosis was 224.1 ml in FEV1 and 123.6 ml in FVC; with tuberculosis 347.4 ml in FEV1 and 264.3 ml in FVC. CONCLUSION: Despite a healthy worker effect, lung function loss was demonstrable whether due to silicosis, tuberculosis or an independent effect of dust. A miner working at a respirable dust intensity of 0.37 mg/m(3) for 30 years would lose on average an additional 208 ml in FVC (95% CI 3, 412) in the absence of other disease, an impact greater than that of silicosis and comparable to that of tuberculosis. Improved dust control on the South African gold mines would reduce the risk of silicosis, tuberculosis and lung function impairment.

Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study.

BACKGROUND: There has been concern that children with variant Creutzfeldt-Jakob disease (vCJD) might be misdiagnosed as cases of Alpers' syndrome, as a spongiform degeneration of the brain is seen in both conditions. OBJECTIVE: To report a national prospective surveillance study of children with progressive intellectual and neurological deterioration, designed to detect any children in the United Kingdom with vCJD, to see whether this misdiagnosis is occurring. METHODS: A monthly surveillance card is sent by the British Paediatric Surveillance Unit to all consultant paediatricians in the UK. The card lists the disorders currently under surveillance. Paediatricians are asked to return the card, reporting cases seen in the previous month. The BPSU office informs the surveillance groups about reported cases, and they obtain clinical information from the notifying paediatrician. RESULTS: After 5 years and 8 months of surveillance, 1244 children had been reported to the study. Alpers' syndrome was confirmed in two, although this was the suggested diagnosis in 11 children at the time of initial notification. CONCLUSIONS: The results show that Alpers' syndrome is rare and it is unlikely that vCJD cases are being misdiagnosed as Alpers' syndrome.

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers.

BACKGROUND AND PURPOSE: Radiation therapy is often the primary treatment for advanced cases of head and neck cancers not considered suitable for radical surgery. In these cases locoregional tumour control rates are low and has warranted innovative treatment modifications, such as altered fractionation schedules and combination with chemotherapy. PATIENTS AND METHODS: From October 1990 to December 1997, 239 patients with squamous cell cancers originating in the head and neck region were randomized to one of three treatment options. Standard therapy consisting of conventional fractionation with 70 Gy in 7 weeks in 35 fractions (CF). The second treatment option consisted of a continuous hyperfractionated accelerated radiotherapy delivering a total dose of 55.3 Gy in 33 fractions over 17 consecutive days (V-CHART). The third study arm had identical fractionation and dose as the above accelerated treatment, with the additional administration of 20 mg/m(2) mitomycin C (MMC) on day 5 of treatment (V-CHART+MMC). RESULTS: Main toxicity resulted from accelerated fractionation in confluent mucositis (Grade 3-4 in 95%) requiring nasogastral tube feeding, analgetics and antiphlogistics in the majority of cases. Haematological toxicity Grade 3-4 was seen after MMC administration in 18%. MMC administration did not influence mucosal reaction. Overall duration of mucositis was not different in the three treatment groups. Loco-regional tumour control was 31% after CF, 32% after V-CHART and 48% after V-CHART+MMC, respectively (P<0.05). Overall crude survival was 24% after CF, 31% following V-CHART and 41% after V-CHART+MMC, respectively (P<0.05). Median follow up was 48 months (assessment performed in February 1999). CONCLUSION: Following shortening overall treatment time from 7 weeks to 17 consecutive days and dose of radiotherapy from 70 to 55.3 Gy the results in the radiotherapy only treated patients are identical. A significant improvement regarding local tumour control and survival was seen following administration of MMC to the accelerated fractionated treatment.

[The value of diffusion-weighted MRT in assessing the bone marrow changes in vertebral metastases]. / Wertigkeit der diffusionsgewichteten MRT in der Beurteilung von Knochenmarkveränderungen bei Wirbelkörpermetastasen.

AIM OF THE STUDY: The aim of the study was the evaluation of the diffusion coefficient (ADC) of vertebral metastasis and regular vertebral bodies with diffusion weighted MRI (DWI). DWI evaluates the tissue-specific molecular diffusion of protons. In tissues with high cell densities (neoplasm) a decreased ADC can be expected due to restricted diffusion according to an exaggerated amount of intra- and intercellular membranes (i.e. diffusion barriers). METHODS: In 5 breast cancer patients the ADC of both known vertebral metastases and of adjacent regular vertebral bodies were measured with DWI (1.0 T; Phased-Array-Body-Coil; b: 880 and 440 s/mm2). RESULTS: The ADC of regular vertebral bodies (1.3 +/- 0.23 x 10(-3) s/mm2) was significantly (p < or = 0.0002) higher than in vertebral metastases (0.39 +/- 0.11 x 10(-3) s/mm2). CONCLUSIONS: These data demonstrate that the ADC can be reliably measured in vertebral bodies. The quantitative evaluation of the ADC in vertebral bodies seems to be an objective and comparable parameter for differentiating malign from benign vertebral tissue.