290 research outputs found
Formation of New Inhibitory Circuits for Treating Temporal Lobe Epilepsy
Take Home Message:
Stem Cell Transplants induce structural plasticity after transplantation into the Hippocampus.
Structural and functional changes may be the mechanism for seizure suppression in Temporal Lobe Epilepsy
Presentation: 40:29
NOTE: PowerPoint slides for presentation are located at bottom of this page
GABAergic Synapse Dysfunction and Repair in Temporal Lobe Epilepsy
Severe medial temporal lobe epilepsy (mTLE) is often associated with pharmacoresistant seizures, impaired memory and mood disorders. In the hippocampus, GABAergic inhibitory interneuron dysfunction and other neural circuit abnormalities contribute to hyperexcitability, but the mechanisms are still not well understood. Experimental approaches aimed at correcting deficits in hippocampal circuits in mTLE include attempts to replace GABAergic interneurons through neural stem cell transplantation. Evidence from studies in rodent mTLE models indicates that transplanted GABAergic progenitor cells integrate into the hippocampus, form inhibitory synapses, reduce seizures and improve cognitive deficits. Here, we review current work in this field and describe potential molecular mechanisms underlying successful transplantation
Cortical GABAergic Interneuron/Progenitor Transplantation as a Novel Therapy for Intractable Epilepsy
Epilepsy is a severe neurological disease affecting more than 70 million people worldwide that is characterized by unpredictable and abnormal electrical discharges resulting in recurrent seizures. Although antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment for seizure control, about one third of patients with epilepsy suffer from intractable seizures that are unresponsive to AEDs. Furthermore, the patients that respond to AEDs typically experience adverse systemic side effects, underscoring the urgent need to develop new therapies that target epileptic foci rather than more systemic interventions. Neurosurgical removal of affected brain tissues or implanting neurostimulator devices are effective options only for a fraction of patients with drug-refractory seizures, so it is imperative to develop treatments that are more generally applicable and restorative in nature. Considering the abnormalities of GABAergic inhibitory interneurons in epileptic brain tissues, one strategy with considerable promise is to restore normal circuit function by transplanting GABAergic interneurons/progenitors into the seizure focus. In this review, we focus on recent studies of cortical GABAergic interneuron transplantation to treat epilepsy and discuss critical issues in moving this promising experimental therapeutic treatment into clinic
A Density Functional Study of Atomic Hydrogen and Oxygen Chemisorption on the Relaxed (0001) Surface of Double Hexagonal Close Packed Americium
Ab initio total energy calculations within the framework of density
functional theory have been performed for atomic hydrogen and oxygen
chemisorption on the (0001) surface of double hexagonal packed americium using
a full-potential all-electron linearized augmented plane wave plus local
orbitals method. Chemisorption energies were optimized with respect to the
distance of the adatom from the relaxed surface for three adsorption sites,
namely top, bridge, and hollow hcp sites, the adlayer structure corresponding
to coverage of a 0.25 monolayer in all cases. Chemisorption energies were
computed at the scalar-relativistic level (no spin-orbit coupling NSOC) and at
the fully relativistic level (with spin-orbit coupling SOC). The two-fold
bridge adsorption site was found to be the most stable site for O at both the
NSOC and SOC theoretical levels with chemisorption energies of 8.204 eV and
8.368 eV respectively, while the three-fold hollow hcp adsorption site was
found to be the most stable site for H with chemisorption energies of 3.136 eV
at the NSOC level and 3.217 eV at the SOC level. The respective distances of
the H and O adatoms from the surface were found to be 1.196 Ang. and 1.164 Ang.
Overall our calculations indicate that chemisorption energies in cases with SOC
are slightly more stable than the cases with NSOC in the 0.049-0.238 eV range.
The work functions and net magnetic moments respectively increased and
decreased in all cases compared with the corresponding quantities of bare dhcp
Am (0001) surface. The partial charges inside the muffin-tins, difference
charge density distributions, and the local density of states have been used to
analyze the Am-adatom bond interactions in detail. The implications of
chemisorption on Am 5f electron localization-delocalization are also discussed.Comment: 9 Tables, 5 figure
Magnetic state of plutonium ion in metallic Pu and its compounds
By LDA+U method with spin-orbit coupling (LDA+U+SO) the magnetic state and
electronic structure have been investigated for plutonium in \delta and \alpha
phases and for Pu compounds: PuN, PuCoGa5, PuRh2, PuSi2, PuTe, and PuSb. For
metallic plutonium in both phases in agreement with experiment a nonmagnetic
ground state was found with Pu ions in f^6 configuration with zero values of
spin, orbital, and total moments. This result is determined by a strong
spin-orbit coupling in 5f shell that gives in LDA calculation a pronounced
splitting of 5f states on f^{5/2} and f^{7/2} subbands. A Fermi level is in a
pseudogap between them, so that f^{5/2} subshell is already nearly completely
filled with six electrons before Coulomb correlation effects were taken into
account. The competition between spin-orbit coupling and exchange (Hund)
interaction (favoring magnetic ground state) in 5f shell is so delicately
balanced, that a small increase (less than 15%) of exchange interaction
parameter value from J_H=0.48eV obtained in constrain LDA calculation would
result in a magnetic ground state with nonzero spin and orbital moment values.
For Pu compounds investigated in the present work, predominantly f^6
configuration with nonzero magnetic moments was found in PuCoGa5, PuSi2, and
PuTe, while PuN, PuRh2, and PuSb have f^5 configuration with sizeable magnetic
moment values. Whereas pure jj coupling scheme was found to be valid for
metallic plutonium, intermediate coupling scheme is needed to describe 5f shell
in Pu compounds. The results of our calculations show that both spin-orbit
coupling and exchange interaction terms in the Hamiltonian must be treated in a
general matrix form for Pu and its compounds.Comment: 20 pages, LaTeX; changed discussion on reference pape
Female bone physiology resilience in 750-300 BP ‘Polynesian Outlier’ community
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in n = 69 individuals from 750 – 300 BP Taumako in Solomon Islands, a remote ‘Polynesian Outlier’ island in Melanesia. We tested whether bone remodelling indicators differed between age-at-death groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-to-osteon (~10%) did not differ between the sexes. Compared to males, the femora of Taumako females experienced higher frequencies of remodelling events, which mirrors bone health paradigms through the life-course today. However, contrary to modern populations, female femoral bone tissue did not decline with age. This matches findings in other archaeological samples, and is testament to ancient female bone physiology resilience also in the Pacific region.Introduction - The importance of bone remodelling through human life-course - Bone remodelling in archaeological humans Results - Trends in bone remodelling at Taumako Discussion - Sex-specific trends in cortical bone remodelling - Bone remodelling with age at Taumako Limitations and remarks on temporal and spatial data Conslusions Materials and Method
Female bone physiology resilience in a past Polynesian Outlier community
Remodelling is a fundamental biological process involved in the maintenance of bone physiology and function. We know that a range of health and lifestyle factors can impact this process in living and past societies, but there is a notable gap in bone remodelling data for populations from the Pacific Islands. We conducted the first examination of femoral cortical histology in 69 individuals from ca. 440–150 BP Taumako in Solomon Islands, a remote ‘Polynesian Outlier’ island in Melanesia. We tested whether bone remodelling indicators differed between age groups, and biological sex validated using ancient DNA. Bone vascular canal and osteon size, vascular porosity, and localised osteon densities, corrected by femoral robusticity indices were examined. Females had statistically significantly higher vascular porosities when compared to males, but osteon densities and ratios of canal-osteon (~ 8%) did not differ between the sexes. Our results indicate that, compared to males, localised femoral bone tissue of the Taumako females did not drastically decline with age, contrary to what is often observed in modern populations. However, our results match findings in other archaeological samples—a testament to past female bone physiology resilience, also now observed in the Pacific region.Introduction - Bone remodelling through human life‑course. - Bone remodelling in archaeological humans. Results - Femoral vascular porosity and bone remodelling indicators at Taumako. Discussion - Sex and cortical bone histology at Taumako. - The effect of age on bone histology at Taumako. Remarks on temporal and spatial bone histology data Limitations Conclusions Materials and method
Patient-reported experiences of cancer care related to the COVID-19 pandemic in Switzerland.
This study aims to describe the experience of Swiss oncological patients during the COVID-19 pandemic.
A national multi-center study including five hospitals covering the three main language regions of Switzerland was conducted between March and July 2021. Patients with melanoma, breast, lung, or colon cancer receiving active systemic anti-cancer treatment at the time of the COVID-19 pandemic were included. We conducted semi-structured telephone or onsite interviews alongside the administration of distress and resilience-validated questionnaires. Thematic analysis was performed for the qualitative data and descriptive statistics for the quantitative data.
Sixty-two cancer patients with a mean age of 61 (SD=14) (58% female) were interviewed. Based on the interviews, we identified that the experience of having cancer during the COVID-19 pandemic was related to five dimensions: psychological, social, support, healthcare, and vaccination. Three themes transverse the five dimensions: (a) needs, (b) positive changes, and (c) phases of the pandemic. In general, patients did not experience delays or disruptions in their cancer treatment nor felt additionally burdened by the pandemic. Lockdown and isolation were reported as mixed experiences (positive and negative), and access to vaccination reassured patients against the risk of infection and instilled hope to return to normalcy. Additionally, we found low distress levels (M=2.9; SD=2.5) and high resilience scores (M=7; SD=1.3) in these patients.
Swiss patients with cancer did not express major needs or disruptions in their care during this period of the COVID-19 pandemic. Results identify the mixed experiences of patients and highlight the high resilience levels
Long-Term Seizure Suppression and Optogenetic Analyses of Synaptic Connectivity in Epileptic Mice with Hippocampal Grafts of GABAergic Interneurons
Studies in rodent epilepsy models suggest that GABAergic interneuron progenitor grafts can reduce hyperexcitability and seizures in temporal lobe epilepsy (TLE). Although integration of the transplanted cells has been proposed as the underlying mechanism for these disease-modifying effects, prior studies have not explicitly examined cell types and synaptic mechanisms for long-term seizure suppression. To address this gap, we transplanted medial ganglionic eminence (MGE) cells from embryonic day 13.5 VGAT-Venus or VGAT-ChR2-EYFP transgenic embryos into the dentate gyrus (DG) of adult mice 2 weeks after induction of TLE with pilocarpine. Beginning 3–4 weeks after status epilepticus, we conducted continuous video-electroencephalographic recording until 90–100 d. TLE mice with bilateral MGE cell grafts in the DG had significantly fewer and milder electrographic seizures, compared with TLE controls. Immunohistochemical studies showed that the transplants contained multiple neuropeptide or calcium-binding protein-expressing interneuron types and these cells established dense terminal arborizations onto the somas, apical dendrites, and axon initial segments of dentate granule cells (GCs). A majority of the synaptic terminals formed by the transplanted cells were apposed to large postsynaptic clusters of gephyrin, indicative of mature inhibitory synaptic complexes. Functionality of these new inhibitory synapses was demonstrated by optogenetically activating VGAT-ChR2-EYFP-expressing transplanted neurons, which generated robust hyperpolarizations in GCs. These findings suggest that fetal GABAergic interneuron grafts may suppress pharmacoresistant seizures by enhancing synaptic inhibition in DG neural circuits
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