Porohyperelastic anatomical models for hydrocephalus and idiopathic intracranial hypertension

This is the accepted manuscript of a paper published in the Journal of Neurosurgery, Published online February 6, 2015; DOI: 10.3171/2014.12.JNS14516.OBJECT Brain deformation can be seen in hydrocephalus and idiopathic intracranial hypertension (IIH) via medical images. The phenomenology of local effects, brain shift, and raised intracranial pressure and herniation are textbook concepts. However, there are still uncertainties regarding the specific processes that occur when brain tissue is subject to the mechanical stress of different temporal and spatial profiles of the 2 neurological disorders. Moreover, recent studies suggest that IIH and hydrocephalus may be diseases with opposite pathogenesis. Nevertheless, the similarities and differences between the 2 subjects have not been thoroughly investigated. METHODS An anatomical porohyperelastic finite element model was used to assess the brain tissue responses associated with hydrocephalus and IIH. The same set of boundary conditions, with the exception of brain loading for development of the transmantle pressure gradient, was applied for the 2 models. The distribution of stress and strain during tissue distortion is described by the mechanical parameters. RESULTS The results of both the hydrocephalus and IIH models correlated with pathological characteristics. For the hydrocephalus model, periventricular edema was associated with the presence of positive volumetric strain and void ratio in the lateral ventricle horns. By contrast, the IIH model revealed edema across the cerebral mantle, including the centrum semiovale, with a positive void ratio and volumetric strain. CONCLUSIONS The model simulates all the clinical features in correlation with the MR images obtained in patients with hydrocephalus and IIH, thus providing support for the role of the transmantle pressure gradient and capillary CSF absorption in CSF-related brain deformation. The finite element methods can be used for a better understanding of the pathophysiological mechanisms of neurological disorders associated with parenchymal volumetric fluctuation.Dr. M. Czosnyka is a consultant for J&J (Codman), and has received payment for lectures from Integra Lifescience. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRFK) funded by the Ministry of Science, ICT, & Future Planning (2013R1A1A1004827); and the International Research & Development Program of the NRFK funded by the Ministry of Education, Science, and Technology of Korea (Grant No. 2014K1A3A1A21001366)

Finite element analysis for normal pressure hydrocephalus: The effects of the integration of sulci.

Finite element analysis (FEA) is increasingly used to investigate the brain under various pathological changes. Although FEA has been used to study hydrocephalus for decades, previous studies have primarily focused on ventriculomegaly. The present study aimed to investigate the pathologic changes regarding sulcal deformation in normal pressure hydrocephalus (NPH). Two finite element (FE) models-an anatomical brain geometric (ABG) model and the conventional simplified brain geometric (SBG) model-of NPH were constructed. The models were constructed with identical boundary conditions but with different geometries. The ABG model contained details of the sulci geometry, whereas these details were omitted from the SBG model. The resulting pathologic changes were assessed via four biomechanical parameters: pore pressure, von Mises stress, pressure, and void ratio. NPH was induced by increasing the transmantle pressure gradient (TPG) from 0 to a maximum of 2.0 mmHg. Both models successfully simulated the major features of NPH (i.e., ventriculomegaly and periventricular lucency). The changes in the biomechanical parameters with increasing TPG were similar between the models. However, the SBG model underestimated the degree of stress across the cerebral mantle by 150% compared with the ABG model. The SBG model also overestimates the degree of ventriculomegaly (increases of 194.5% and 154.1% at TPG = 2.0 mmHg for the SBG and ABG models, respectively). Including the sulci geometry in a FEA for NPH clearly affects the overall results. The conventional SBG model is inferior to the ABG model, which accurately simulated sulcal deformation and the consequent effects on cortical or subcortical structures. The inclusion of sulci in future FEA for the brain is strongly advised, especially for models used to investigate space-occupying lesions.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013R1A1A1004827).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.media.2015.05.00

Evaluation of an on-line reflective journal in engineering education

Reflective thinking based on experiential learning is a key skill for the professional engineer. The use of a reflective learning journal is thought to be a valuable tool in developing reflexivity. An evaluation was undertaken of student perceptions of an on-line reflective journal introduced into an engineering management study unit.<br /

The response of the tandem pore potassium channel TASK-3 (K2P9.1) to voltage : gating at the cytoplasmic mouth

Although the tandem pore potassium channel TASK-3 is thought to open and shut at its selectivity filter in response to changes of extracellular pH, it is currently unknown whether the channel also shows gating at its inner, cytoplasmic mouth through movements of membrane helices M2 and M4.We used two electrode voltage clamp and single channel recording to show that TASK-3 responds to voltage in a way that reveals such gating. In wild-type channels, Popen was very low at negative voltages, but increased with depolarisation. The effect of voltage was relatively weak and the gating charge small, ∼0.17.Mutants A237T (in M4) and N133A (in M2) increased Popen at a given voltage, increasing mean open time and the number of openings per burst. In addition, the relationship between Popen andvoltagewas shifted to lesspositive voltages. Mutation of putative hinge glycines (G117A, G231A), residues that are conserved throughout the tandem pore channel family, reduced Popen at a given voltage, shifting the relationship with voltage to a more positive potential range. None of these mutants substantially affected the response of the channel to extracellular acidification. We have used the results from single channel recording to develop a simple kinetic model to show how gating occurs through two classes of conformation change, with two routes out of the open state, as expected if gating occurs both at the selectivity filter and at its cytoplasmic mouth

Nocardia kroppenstedtii sp. nov., a novel actinomycete isolated from a lung transplant patient with a pulmonary infection

An actinomycete, strain N1286T, isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. It was most closely related to Nocardia farcinica DSM 43665T (99.8% gene similarity) but was distinguished from the latter by a low level of DNA:DNA relatedness. These strains were also distinguished by a broad range of phenotypic properties. On the basis of these data, it is proposed that isolate N1286T (=DSM 45810T = NCTC 13617T) should be classified as the type strain of a new Nocardia species for which the name Nocardia kroppenstedtii is proposed

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

One-year urinary and sexual outcome trajectories among prostate cancer patients treated by radical prostatectomy: A prospective study

BACKGROUND: To examine one-year trajectories of urinary and sexual outcomes, and correlates of these trajectories, among prostate cancer patients treated by radical prostatectomy (RP). METHODS: Study participants were recruited from 2011 to 2014 at two US institutions. Self-reported urinary and sexual outcomes were measured at baseline before surgery, and 5 weeks, 6 months and 12 months after surgery, using the modified Expanded Prostate Cancer Index Composite-50 (EPIC-50). Changes in EPIC-50 scores from baseline were categorized as improved (beyond baseline), maintained, or impaired (below baseline), using previously-reported minimum clinically important differences. RESULTS: Of the 426 eligible participants who completed the baseline survey, 395 provided data on at least one EPIC-50 sub-scale at 5 weeks and 12 months, and were analyzed. Although all mean EPIC-50 scores declined markedly 5 weeks after surgery and then recovered to near (incontinence-related outcomes) or below (sexual outcomes) baseline levels by 12 months post-surgery, some men experienced improvement beyond their baseline levels on each sub-scale (3.3-51% depending on the sub-scale). Having benign prostatic hyperplasia (BPH) at baseline (prostate size ≥ 40 g; an International Prostate Symptom Index Score ≥ 8; or using BPH medications) was associated with post-surgical improvements in voiding dysfunction-related bother at 5 weeks (OR = 3.9, 95% CI: 2.1-7.2) and 12 months (OR = 3.3, 95% CI: 2.0-5.7); and in sexual bother at 5 weeks (OR = 5.7, 95% CI:1.7-19.3) and 12 months (OR = 3.0, 95% CI: 1.2-7.1). CONCLUSIONS: Our findings provide additional support for considering baseline BPH symptoms when selecting the best therapy for early-stage prostate cancer