Non-viral delivery of an optogenetic tool into cells with self-healing hydrogel

Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Fu-Yu Hsieh, Hao-Wei Han, Xiao-Ru Chen, Chii-Shen Yang, Yen Wei, Shan-hui Hsu
Optogenetics offers unique, temporally precise control of neural activity in genetically targeted specific neurons that express light-sensitive opsin molecules. Three-dimensional (3D) delivery of optogenetics can be realized by co-injection of bacteriorhodopsin (HEBR) plasmid with a chitosan-based self-healing hydrogel with strong shear-thinning properties. The HEBR protein shows photoelectrical properties and can be used as an optical switch for cell activation. We optimize the shear force generated during the process of injection (∼100 Pa), which is transient because of the self-healing nature of the hydrogel. This transient force exerted by the self-healing hydrogel may allow the cytosolic delivery of HEBR plasmid with excellent cell viability and a high efficiency approaching 80%. When excited with green light, HEBR-delivered neural stem cells (NSCs) can proliferate and specifically differentiate into neurons in vitro and rescue the function of nerve impaired zebrafish in vivo. This novel optogenetic method combining 3D injectable self-healing hydrogel offers potential temporal-spatial approaches to treat neurodegenerative diseases in the future.



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Walking the line: The fate of nanomaterials at biological barriers

Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Huan Meng, Wei Leong, Kam W. Leong, Chunying Chen, Yuliang Zhao
Biological systems have developed an efficient multi-tiered defense system to block foreign substances such as engineered nanomaterials (NMs) from causing damage. In a pathological scenario, the disease itself may also pose additional barriers due to the imbalance between abnormal cells and their surrounding microenvironment, and NMs could behave similarly or differently to classic foreign substances, depending on their unique characteristics. Thus, understanding the mechanisms that govern the fate of NMs against these biological barriers, including the strategies that can be used to shift their fate between access and blockage, become key information for NMs design. In this manuscript, we first describe the biological barriers that NMs may encounter, and further discuss how these biological barrier interactions could shift the fate of NMs between toxicity and therapeutic potential. A list of effects that may influence NMs access at nano/bio interface are presented and discussed, followed by personal insights on the important nano/bio topics that require additional research for a better understanding of NM/biological barrier interactions.



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Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy

Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): Ling-xiao Zhang, Xi-xiu Xie, Dong-qun Liu, Zhi Ping Xu, Rui-tian Liu
Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and CpG onto LDH nanoparticles. Using melanoma as the model cancer and Tyrosinase-related protein 2 (Trp2) peptide as the model antigen, we demonstrated that dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth in comparison with aggregated LDH-based vaccine. We further constructed multi-target dispersion-stable LDH-based vaccine by co-loading Trp2, two mutated epitopes (M27 and M30) and CpG, which showed remarkable inhibition of melanoma growth. These results suggest that dispersion-stable LDH nanoparticles are an ideal platform to load multi-antigens and immune stimulants as effective personalized therapeutic cancer vaccines.

Graphical abstract

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Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results also showed that targeted delivery of siRNA specific for CD44 can efficiently overcome resistance to EGFR targeting in TNBC cells both in vitro and in vivo. Overall, our results establish a new principle to achieve EGFR inhibition in TNBC and limit drug resistance.



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Hydroxycoumarins: New, effective plant-derived compounds reduce Ralstonia pseudosolanacearum populations and control tobacco bacterial wilt

Publication date: Available online 17 May 2018
Source:Microbiological Research
Author(s): Liang Yang, Lintong Wu, Xiaoyuan Yao, Shiyuan Zhao, Jiao Wang, Shili Li, Wei Ding
Plant wilt disease caused by the soilborne bacterial pathogen Ralstonia pseudosolanacearum is one of the most devastating plant diseases; however, no effective protection against this disease has been developed. Coumarins are important natural plant-derived compounds with a wide range of bioactivities and extensive applications in medicine and agriculture. In the present study, three hydroxycoumarins (Hycs), umbelliferone (UM), esculetin (ES) and daphnetin (DA) significantly inhibited the growth of R. pseudosolanacearum on solid medium in a concentration-dependent manner, and the minimum inhibitory concentration (MICs) of these compounds was 325 mg·L⁻¹, 125 mg·L⁻¹ and 75 mg·L⁻¹, respectively. The percentage of live cells of R. pseudosolanacearum when supplemented with UM, ES, and DA was 63.61%, 17.81% and 7.23%, respectively, which were significantly lower than the DMSO treatment with 92%. Furthermore, irrigating roots with hydroxycoumarins (Hycs) 24 h before inoculation with R. pseudosolanacearum significantly delayed the occurrence of tobacco bacterial wilt, with the control efficiency of the DA treatment (the most efficient of Hycs treatment) 80.03%, 69.83%, 59.19%, 45.49%, 44.12%, 38.27% at 6, 8, 10, 12, 14, and 16 days after inoculation, respectively. Compared with the DMSO treatment, the pathogen populations of tobacco stems supplemented with 100 mg L⁻¹ DA were the lowest, with population significantly reduced by 22.46%, 27.34%, and 18.06% at 4, 7, and 10 days after inoculation, respectively. Based on this study, these Hycs could be applied as potential protective agents in the management of tobacco bacterial wilt.



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Masthead

Publication date: May–June 2018
Source:Brachytherapy, Volume 17, Issue 3





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Table of Contents

Publication date: May–June 2018
Source:Brachytherapy, Volume 17, Issue 3





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A Novel Approach to Probabilistic Characterisation of Neural Firing Patterns

Publication date: Available online 17 May 2018
Source:Journal of Neuroscience Methods
Author(s): Gorana Mijatović, Tatjana Lončar-Turukalo, Emmanuel Procyk, Dragana Bajić
BackgroundThe advances in extracellular neural recording techniques result in big data volumes that necessitate fast, reliable, and automatic identification of statistically similar units. This study proposes a single framework yielding a compact set of probabilistic descriptors that characterise the firing patterns of a single unit.New MethodProbabilistic features are estimated from an inter-spike-interval time series, without assumptions about the firing distribution or the stationarity. The first level of proposed firing patterns decomposition divides the inter-spike intervals into bursting, moderate and idle firing modes, yielding a coarse feature set. The second level identifies the successive bursting spikes, or the spiking acceleration/deceleration in the moderate firing mode, yielding a refined feature set. The features are estimated from simulated data and from experimental recordings from the lateral prefrontal cortex in awake, behaving rhesus monkeys.ResultsAn efficient and stable partitioning of neural units is provided by the ensemble evidence accumulation clustering. The possibility of selecting the number of clusters and choosing among coarse and refined feature sets provides an opportunity to explore and compare different data partitions.ConclusionsThe estimation of features, if applied to a single unit, can serve as a tool for the firing analysis, observing either overall spiking activity or the periods of interest in trial-to-trial recordings. If applied to massively parallel recordings, it additionally serves as an input to the clustering procedure, with the potential to compare the functional properties of various brain structures and to link the types of neural cells to the particular behavioural states.

Graphical abstract

Highlights

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Longitudinal Observations Using Simultaneous fMRI, Multiple Channel Electrophysiology Recording, and Chemical Microiontophoresis in The Rat Brain

Publication date: Available online 17 May 2018
Source:Journal of Neuroscience Methods
Author(s): Saul Jaime, Jose E. Cavazos, Yihong Yang, Hanbing Lu
BackgroundfMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity.New MethodsSimultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection.ResultsIntracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4 T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) enhanced dopaminergic neuronal activity in the ventral tegmental area (VTA) and altered LFP signal and fMRI functional connectivity in the striatum.Comparisons with Existing Method(s)Nanomanufacturing advances permit the production of MRI-compatible microelectrode arrays (with 16 or more channels), extending research beyond conventional methods limited to fewer channels. Our method permits longitudinal data collection of LFP and rsMRI and our algorithm effectively detects and replaces fMRI-induced electrophysiological noise, permitting rsMRI data collection concomitant with LFP recordings.ConclusionsOur model consists of longitudinal concurrent fMRI and multichannel intracortical electrophysiological recording during microinjection of pharmacological agents to modulate neural activity in the rat brain. We used commercial micro-electrodes and recording system and can be readily generalized to other labs.



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Feasibility of imaging evoked activity throughout the rat brain using electrical impedance tomography

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Mayo Faulkner, Sana Hannan, Kirill Aristovich, James Avery, David Holder
Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 μm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode. Impedance changes of −0.16 ± 0.08% at 12.9 ± 1.4 ms and −0.41 ± 0.14% at 8.8±1.9 ms were recorded from the cortex and VPL respectively. For imaging purposes, two 57-channel epicortical electrode arrays were used with one placed on each hemisphere of the rat brain. Despite using parameters optimised toward measuring thalamic activity and undertaking extensive averaging, reconstructed activity was constrained to the cortical somatosensory forepaw region and no significant activity at a depth greater than 1.6 mm below the surface of the cortex could be reconstructed. An evaluation of the depth sensitivity of EIT was investigated in simulations using estimates of the conductivity change and noise levels derived from experiments. These indicate that EIT imaging with epicortical electrodes is limited to activity occurring 2.5 mm below the surface of the cortex. This depth includes the hippocampus and so EIT has the potential to image activity, such as epilepsy, originating from this structure. To image deeper activity, however, alternative methods such as the additional implementation of depth electrodes will be required to gain the necessary depth resolution.



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Contextualizing action observation in the predictive brain: Causal contributions of prefrontal and middle temporal areas

Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Lucia Amoruso, Alessandra Finisguerra, Cosimo Urgesi
Context facilitates the recognition of forthcoming actions by pointing to which intention is likely to drive them. This intention is thought to be estimated in a ventral pathway linking MTG with frontal regions and to further impact on the implementation of sensory predictions within the action observation network (AON). Additionally, when conflicting intentions are estimated from context, the DLPFC may bias action selection. However, direct evidence for the contribution of these areas to context-embedded action representations in the AON is still lacking. Here, we used a perturb-and-measure TMS-approach to disrupt neural activity, separately in MTG and DLPFC and subsequently measure cortico-spinal excitability while observing actions embedded in congruent, incongruent or ambiguous contexts. Context congruency was manipulated in terms of compatibility between observed kinematics and the action goal suggested by the ensemble of objects depicted in the environment. In the control session (vertex), we found an early facilitation and later inhibition for kinematics embedded in congruent and incongruent contexts, respectively. MTG stimulation altered the differential modulation of M1 response to congruent vs. incongruent contexts, suggesting this area specifies prior representations about appropriate object graspability. Interestingly, all effects were abolished after DLPFC stimulation highlighting its critical role in broader contextual modulation of the AON activity.



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Response of the multiple-demand network during simple stimulus discriminations

Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Tanya Wen, Daniel J. Mitchell, John Duncan
The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control.



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Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits

Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Marta Brocka, Cornelia Helbing, Daniel Vincenz, Thomas Scherf, Dirk Montag, Jürgen Goldschmidt, Frank Angenstein, Michael Lippert
Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data.



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Oscillatory networks of high-level mental alignment: A perspective-taking MEG study

Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): R.A. Seymour, H. Wang, G. Rippon, K. Kessler
Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3–7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations.



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The neural basis of free language choice in bilingual speakers: Disentangling language choice and language execution

Publication date: 15 August 2018
Source:NeuroImage, Volume 177
Author(s): Carlo Reverberi, Anna K. Kuhlen, Shima Seyed-Allaei, R.Stefan Greulich, Albert Costa, Jubin Abutalebi, John-Dylan Haynes
For everyday communication, bilingual speakers need to face the complex task of rapidly choosing the most appropriate language given the context, maintaining this choice over the current communicative act, and shielding lexical selection from competing alternatives from non-target languages. Yet, speech production of bilinguals is typically flawless and fluent. Most of the studies available to date constrain speakers' language choice by cueing the target language and conflate language choice with language use. This left largely unexplored the neural mechanisms underlying free language choice, i.e., the voluntary situation of choosing the language to speak. In this study, we used fMRI and Multivariate Pattern Analysis to identify brain regions encoding the target language when bilinguals are free to choose in which language to name pictures. We found that the medial prefrontal cortex encoded the chosen language prior to speaking. By contrast, during language use, language control recruited a wider brain network including the left inferior frontal lobe, the basal ganglia, and the angular and inferior parietal gyrus bilaterally. None of these regions were involved in language choice. We argue that the control processes involved in language choice are different from those involved in language use. Furthermore, our findings confirm that the medial prefrontal cortex is a domain-general region critical for free choice and that bilingual language choice relies on domain general processes.

Graphical abstract

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Scholar : Canadian Water Resources Journal / Revue canadienne des ressources hydriques, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Canadian Water Resources Journal / Revue canadienne des ressources hydriques, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Editors' Note Editors' Note Jim Buttle & Chris Spence Pages: 1-1 | DOI: 10.1080/07011784.2018.1434297 Articles Land-use practices influence nutrient concentrations of southwestern Ontario streams Kathryn E. Thomas, Renee Lazor, Patricia A. Chambers & Adam G. Yates Pages: 2-17 | DOI: 10.1080/07011784.2017.1411211 Influence of riparian grazing on channel morphology and riparian health of the Lower Little Bow River Jim Miller, Tony Curtis, David Chanasyk & Walter Willms Pages: 18-32 | DOI: 10.1080/07011784.2017.1400925 Flood risk management in the Canadian prairie provinces: Defaulting towards flood resistance and recovery versus resilience Alasdair Morrison, Bram F. Noble & Cherie J. Westbrook Pages: 33-46 | DOI: 10.1080/07011784.2018.1428501 Equifinality and automatic calibration: What is the impact of hypothesizing an optimal parameter set on modelled hydrological processes? Étienne Foulon & Alain N. Rousseau Pages: 47-67 | DOI: 10.1080/07011784.2018.1430620 List of Reviewers List of reviewers for papers published in 2017 Pages: 68-68 | DOI: 10.1080/07011784.2018.1434300 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online

The online platform for Taylor & Francis Online content New for Alcheringa: An Australasian Journal of Palaeontology and online now on Taylor & Francis Online: Original Articles Bioerosion traces on titanosaurian sauropod bones from the Upper Cretaceous Marília Formation of Brazil Voltaire Dutra Paes Neto, Heitor Francischini, Agustín Guillermo Martinelli, Thiago Da Silva Marinho, Luiz Carlos Borges Ribeiro, Marina Bento Soares & Cesar Leandro Schultz Pages: 1-12 | DOI: 10.1080/03115518.2018.1456561 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Annals of GIS are available online

The online platform for Taylor & Francis Online content New for Annals of GIS and online now on Taylor & Francis Online: Original Articles Evaluating gender representativeness of location-based social media: a case study of Weibo Yihong Yuan, Guixing Wei & Yongmei Lu Pages: 1-14 | DOI: 10.1080/19475683.2018.1471518 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Hand Sensibility in Healthy Young Children

Publication date: Available online 16 May 2018
Source:Pediatric Neurology
Author(s): Sonja M. Buitenhuis, Willem Pondaag, Ron Wolterbeek, Martijn J.A. Malessy
Aim: The aims of the study were (1) to assess hand sensibility in healthy young children using instruments validated for adults; (2) to identify which test tools are suitable; and (3) to compare the dominant and non-dominant sides.Methods: Twenty-five healthy children aged 7-11 years (mean 9.5 years) were investigated. Sensibility was assessed with the Semmes-Weinstein Monofilament test (SW), two-point discrimination (2PD), localization test (LOC) and stereognosis object recognition (SOR). Sensory stimuli were administered to fingertips.Results: The thinnest SW filament (D; 2.83mm) was felt at 94% of examined points. A 2PD at the smallest distance of 2 mm was found in the thumb in 84% of children and in the index finger in 94%. Only 60% felt this distance in the fifth digit. The difference between little finger and index finger was statistically significant (p= 0.001). Near-maximum value on the LOC was scored in both hands. All children had a 100% score for both hands in the SOR.Interpretation: Most children can detect touch in the digits at low pressure. The majority are able to discern two points 2 mm apart in the first and second digits, but significantly less so in the fifth digit. Children are well able to localize on which side of a fingertip pressure is applied. Objects are recognized very well, and occasionally too quickly to record. There appear to be no differences between the dominant and non-dominant hands in either test. Adjustment of sensory test protocols routinely used in adults is necessary to optimize hand sensation testing in children, in view of the detection limits.



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Continuous low-dose antibiotic prophylaxis to prevent urinary tract infection in adults who perform clean intermittent self-catheterisation: the AnTIC RCT.

Continuous low-dose antibiotic prophylaxis reduced the frequency of symptomatic, antibiotic-treated urinary tract infection by 48%, although antimicrobial resistance of bacteria isolated from the urine of those taking prophylaxis increased

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