Barbed channels enhance unidirectional connectivity between neuronal networks cultured on multi electrode arrays.

Cultured neurons on multi electrode arrays (MEAs) have been widely used to study various as-pects of neuronal (network) functioning. A possible drawback of this approach is the lack of struc-ture in these networks. At the single cell level, several solutions have been proposed to enable di-rected connectivity, and promising results were obtained. At the level of connected sub-populations, a few attempts have been made with promising results. First assessment of the de-signs’ functionality, however, suggested room for further improvement.\ud We designed a two chamber MEA aiming to create a unidirectional connection between the net-works in both chambers (‘emitting’ and ‘receiving’). To achieve this unidirectionality, all intercon-necting channels contained barbs that hindered axon growth in the opposite direction (from receiv-ing to emitting chamber). Visual inspection showed that axons predominantly grew through the channels in the promoted direction. This observation was confirmed by spontaneous activity re-cordings. Cross-correlation between the signals from two electrodes inside the channels suggested signal propagation at ≈2 m/s from emitting to receiving chamber. Cross-correlation between the fir-ing patterns in both chambers indicated that most correlated activity was initiated in the emitting chamber, which was also reflected by a significantly lower fraction of partial bursts (e. a one-chamber-only burst) in the emitting chamber. Finally, electrical stimulation in the emitting chamber induced a fast response in that chamber, and a slower response in the receiving chamber. Stimula-tion in the receiving chamber evoked a fast response in that chamber, but no response in the emit-ting chamber. These results confirm the predominantly unidirectional nature of the connecting channels from emitting to receiving chamber

The burden of parenting children with frontal lobe epilepsy

Objective: Caring for a child with a chronic illness adds stress to the typical parenting stress in healthy developing children. This stress can place a heavy burden on parents and may increase when a child displays problem behavior. In general, parenting and child's behavior problems are associated. Furthermore, externalizing (more outgoing) behavior is reported frequently in children with frontal lobe epilepsy (FLE). Therefore, in this study, we first investigated the burden of parents of children with FLE, and second, we investigated the relation between the experienced burden and reported behavioral problems. The validity of parents' reports on proxy measures as well as duration of epilepsy is taken into account.Methods: Thirty-one parents of children with FLE completed validated questionnaires about behavioral problems and burden of parenting. To examine if parents tend to be inconsistent or unusually negative, we used the two validity scales of the Behavioral Rating Inventory of Executive Function (BRIEF) (Negativity and Inconsistency).Results: Only parents of children with FLE who have had epilepsy for 5 years or longer report more problems on the Nijmeegse Vragenlijst voor de Opvoedingssituatie (NVOS) subscales 'Able to manage', 'Child is a burden', and 'Good Interaction' compared with the healthy controls. The subscale 'Child is a burden' significantly predicts scores in about 20% to 49% on the main scales of the Child Behavior Checklist (CBCL), the Global Executive Composite (GEC), and Behavioral Regulation Index (BRI) of the BRIEF. Only 6% of parents scored in the dinical range of the negativity scale of the BRIEF. For the inconsistency scale, this was 45%.Conclusion: Parents of children with FLE do not report excessive parental burden. Longer duration of epilepsy might be a risk factor in experiencing burden. The findings suggest a link between parental burden and behavioral problems in children with FLE. Externalizing behavioral problems are the most marked behavioral problems, which relate to the parental burden. Parents tend to be inconsistent in their ratings. (C) 2019 Elsevier Inc. All rights reserved.</p

The burden of parenting children with frontal lobe epilepsy

Objective: Caring for a child with a chronic illness adds stress to the typical parenting stress in healthy developing children. This stress can place a heavy burden on parents and may increase when a child displays problem behavior. In general, parenting and child's behavior problems are associated. Furthermore, externalizing (more outgoing) behavior is reported frequently in children with frontal lobe epilepsy (FLE). Therefore, in this study, we first investigated the burden of parents of children with FLE, and second, we investigated the relation between the experienced burden and reported behavioral problems. The validity of parents' reports on proxy measures as well as duration of epilepsy is taken into account. Methods: Thirty-one parents of children with FLE completed validated questionnaires about behavioral problems and burden of parenting. To examine if parents tend to be inconsistent or unusually negative, we used the two validity scales of the Behavioral Rating Inventory of Executive Function (BRIEF) (Negativity and Inconsistency). Results: Only parents of children with FLE who have had epilepsy for 5 years or longer report more problems on the Nijmeegse Vragenlijst voor de Opvoedingssituatie (NVOS) subscales 'Able to manage', 'Child is a burden', and 'Good Interaction' compared with the healthy controls. The subscale 'Child is a burden' significantly predicts scores in about 20% to 49% on the main scales of the Child Behavior Checklist (CBCL), the Global Executive Composite (GEC), and Behavioral Regulation Index (BRI) of the BRIEF. Only 6% of parents scored in the dinical range of the negativity scale of the BRIEF. For the inconsistency scale, this was 45%. Conclusion: Parents of children with FLE do not report excessive parental burden. Longer duration of epilepsy might be a risk factor in experiencing burden. The findings suggest a link between parental burden and behavioral problems in children with FLE. Externalizing behavioral problems are the most marked behavioral problems, which relate to the parental burden. Parents tend to be inconsistent in their ratings. (C) 2019 Elsevier Inc. All rights reserved

Is More Always Better? An Exploration of the Differential Effects of Functional Integration on Performance in New Product Development

N/

Mycophenolate mofetil hampers antibody responses to a broad range of vaccinations in kidney transplant recipients:Results from a randomized controlled study

Objectives: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. Methods: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. Results: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54–66) years old, with median eGFR of 54 (44–67) ml/min, tacrolimus trough levels 6.1 (5.4–7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500–2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p &lt; 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). Conclusions: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.</p

Mycophenolate mofetil hampers antibody responses to a broad range of vaccinations in kidney transplant recipients:Results from a randomized controlled study

Objectives: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. Methods: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. Results: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54–66) years old, with median eGFR of 54 (44–67) ml/min, tacrolimus trough levels 6.1 (5.4–7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500–2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p &lt; 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). Conclusions: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.</p

Twofold surface of the decagonal Al-Cu-Co quasicrystal

We have investigated the atomic structure of the twofold surface of the decagonal Al-Cu-Co quasicrystal using scanning tunneling microscopy and low-energy electron diffraction. We have found that most of the surface features can be interpreted using the bulk-structure model proposed by Deloudi and Steurer (S. Deloudi, Ph.D. thesis, ETH, Zürich, 2008). The surface consists of terraces separated by steps of various heights. Step heights and steps sequences match with the thickness and the stacking sequence of blocks of layers separated by gaps in the model. These blocks of layers define possible surface terminations consisting of periodic atomic rows which are aperiodically stacked. These surface terminations are dense (∼10 at./nm2) and are of three types. The first two types are pure or almost pure Al while the third one contains 30–40 at. % of transition-metal atoms. Experimentally, we observe three different types of fine structures on terraces, which can be interpreted using the three possible types of bulk terminations. Terraces containing transition metals exhibit a strong bias dependency and present a doubling of the basic 0.42 nm periodicity, in agreement with the 0.84 nm superstructure of the bulk. In addition, a high density of interlayer phason defects is observed on this surface that could contribute to the stabilization of this system through configurational entropy associated with phason disorder

A method to correlate mRNA expression datasets obtained from fresh frozen and formalin-fixed, paraffin-embedded tissue samples: A matter of thresholds

Background: Gene expression profiling of tumors is a successful tool for the discovery of new cancer biomarkers and potential targets for the development of new therapeutic strategies. Reliable profiling is preferably performed on fresh frozen (FF) tissues in which the quality of nucleic acids is better preserved than in formalin-fixed paraffin-embedded (FFPE) material. However, since snap-freezing of biopsy materials is often not part of daily routine in pathology laboratories, one may have to rely on archival FFPE material. Procedures to retrieve the RNAs from FFPE materials have been developed and therefore, datasets obtained from FFPE and FF materials need to be made compatible to ensure reliable comparisons are possible. Aim: To develop an efficient method to compare gene expression profiles obtained from FFPE and FF samples using the same platform. Methods: Twenty-six FFPE-FF sample pairs of the same tumors representing various cancer types, and two FFPE-FF sample pairs of breast cancer cell lines, were included. Total RNA was extracted and gene expression profiling was carried out using Illumina's Whole-Genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) V3 arrays, enabling the simultaneous detection of 24,526 mRNA transcripts. A sample exclusion criterion was created based on the expression of 11 stably expressed reference genes. Pearson correlation at the probe level was calculated for paired FFPE-FF, and three cut-off values were chosen. Spearman correlation coefficients between the matched FFPE and FF samples were calculated for three probe lists with varying levels of significance and compared to the correlation based on all measured probes. Unsupervised hierarchical cluster analysis was performed to verify performance of the included probe lists to compare matched FPPE-FF samples. Results: Twenty-seven FFPE-FF pairs passed the sample exclusion criterion. From the profiles of 27 FFPE and FF matched samp