Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). in order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions

Micro-machining workstation for a diode pumped Nd:YAG high-brightness laser system

A Nd:YAG micro-machining workstation that allows cutting on a scale of a few microns has been developed and operated. The system incorporates a telescope viewing system that allows control during the work and a software interface to translate AutoCad files. Some examples of the performance are given. With this setup we demonstrate the possibility of machining within a few microns with a Nd:YAG laser

Acoustic analysis of the effect of Personal Protective Equipment on speech understanding: Lessons for clinical environments

Objective:The use of various types of filtering facepiece class 3 (FFP3) mask have become commonplacesince the Covid-19 outbreak. These have been evaluated in terms of efficacy regarding aerosol filtrationbut less emphasis has been placed on the acoustic effects of such masks and their consequences for clin-ical communication. Design:A microphone 65cm from a sound-producing Head and Torso Simulator (wearing the masks)was used to measure attenuation via a tone sweep. Predicted impact on speech reception in noise wasassessed by weighting the attenuations of cochlear excitation patterns by the frequency importance func-tion of the Speech Intelligibility Index. Study sample:We evaluated acoustic attenuation properties of seven FFP3 masks and a Type IIR surgicalmask (as a comparator). Results:The Type IIR mask had the smallest impact on SNR (2.6 dB with visor). Most FFP3s with an add-ition of a visor (if not already face covering) impacted SNR by approximately 6 dB. The 3 M 6000 was sig-nificantly worse (15.8 dB). Conclusions:Mouth-and-nose covering FFP3s masks had similar effects on SNR ( 6.2 dB with visor). TheTecmen TM-H2 had several advantages over other masks evaluated. It was reusable, allowed lipreadingclues and the attenuation was similar to other FFP3s

The structural stability of positive development across young adulthood: longitudinal findings from the Australian temperament project

The purpose of this study was to examine the structural stability of positive development across the 20s using data from one of Australia’s oldest population-based studies of social–emotional development. Positive development was indicated by civic action and engagement, trust and tolerance of others, trust in authorities and organizations, social competence, and life satisfaction. Results extend an earlier published model spanning 19–20 and 23–24 years by incorporating a new wave of data collected at 27–28 years. The age 27–28 latent model was gender invariant and a robust replication of our earlier model. Associations between the latent constructs in the mid- to late 20s were stronger than those in emerging adulthood. This work provides evidence of a cohesive higher order construct of positive development from late adolescence to the late 20s and has the potential to inform measurement of strength-based research and prevention programs in the emerging and young adult periods