Distribution of alpha-amino-3-hydroxy-5-methyl-4 isoazolepropionic acid and N-methyl-D-aspartate receptor subunits in the vestibular and spiral ganglia of the mouse during early development

We investigated the distribution of the glutamate receptor subunits, alpha-amino-3-hydroxy-5-methyl-4 isoazolepropionic acid (AMPA) GluR2 and GluR2/R3, and N-methyl-D-aspartate (NMDA) NR1, and the timing of their appearance during early development of the mouse vestibular and spiral ganglia. NMDA NR1 was the first to be expressed, in the statoacoustic ganglion neurons on E11. GluR2/R3 immunoreactivity was detected in these neurons on E12. This signal probably corresponded exclusively to GluR3, as no signal was obtained for GluR2 alone at this stage. The appearance of these proteins began much earlier than previously reported. GluR2 staining was observed later, on E14 in the vestibular neurons and on E17 in the spiral neurons. The sequence in which these three glutamate receptors appeared suggested possible differences in their roles in the establishment of neuronal circuitry in the inner ear sensory epithelia. The production of NR1 and GluR2/R3 began during the early period of neuron growth and fasciculation. GluR2 appeared later and its expression paralleled synaptogenesis in the vestibular sensory epithelia and in the organ of Corti.     

Facilitated CA1 hippocampal synaptic plasticity in dystrophin‐deficient mice: Role for GABAA receptors?

Duchenne muscular dystrophy (DMD) is associated with cognitive deficits that may result from a deficiency in the brain isoform of the cytoskeletal membrane-associated protein, dystrophin. CA1 hippocampal short-term potentiation (STP) of synaptic transmission is increased in dystrophin-deficient mdx mice, which has been attributed to a facilitated activation of NMDA receptors. In this study, extracellular recordings in the hippocampal slice preparation were used first to determine the consequences of this alteration on short-term depression (STD). STD induction was facilitated in mdx as compared with wild-type mice in a control medium. Because brain dystrophin deficiency results in a decreased number of gamma-aminobutyric acid A (GABAA)-receptor clusters, we tested the hypothesis that neuronal disinhibition contributes to the enhanced synaptic plasticity in mdx mice. We found that the GABAA receptor antagonist, bicuculline, increased basal neurotransmission in wild-type, but not in mdx mice and prevented the enhanced STP and STD in the CA1 area of slices from mdx mice. The possibility that altered GABA mechanisms underlie the facilitation of NMDA receptor-dependent synaptic plasticity in mdx mice is discussed.     

Rapid Push vs Pump-Infused Subcutaneous Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary Immunodeficiency Patients

Purpose

Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient’s life quality index (LQI).

Methods

This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%.

Results

Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p?=?0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump.

Conclusions

Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician’s armamentarium which is preferred by some patients and is cost-effective.

ClinicalTrials.gov Identifier

NCT02180763

Clinical Implications

Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week.

Capsule Summary

This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician’s armamentarium.

     

Effect of cobalt and chromium ions on human MG-63 osteoblasts in vitro: morphology, cytotoxicity, and oxidative stress

Recent studies demonstrated that Co(2+) and Cr(3+) ions induced cell mortality, TNF-alpha secretion, and oxidation of proteins in macrophages. However, little is known about the effects of corrosion products on the osteogenic cells, which have a crucial role in controlling bone remodeling. The aim of the present study was to investigate the effect of Co(2+) (0-10 ppm) and Cr(3+) (0-150 ppm) on human MG-63 osteoblast-like cells in term of cytotoxicity and oxidative stress. Microscopic analysis demonstrated changes in shape, size, and number of cells. Co(2+) had a greater effect on these parameters than Cr(3+). Cell counting showed a significant decrease in the number of MG-63 osteoblasts in a time- and dose-dependent manner, with Co(2+) more toxic than Cr(3+). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis also showed a decreased cellular activity in presence of Co(2+) and Cr(3+) ions. Oxidized and nitrated proteins, two markers of oxidative stress, were detected as single bands and revealed time- and dose-dependent protein modifications. We also studied the expression of three antioxidant enzymes. The expression of heme oxygenase-1 was increased by both ions after 24h, before decreasing gradually thereafter. Glutathione peroxidase expression was also increased in a concentration- and time-dependent manner by both Co(2+) and Cr(3+) ions. Co(2+) decreased catalase expression while Cr(3+) increased it in a dose- and time-dependent manner. In conclusion, this study demonstrated that Cr(3+) and Co(2+) have a cytotoxic effect on MG-63 osteoblasts and have the potential to modify their redox state.     

The music of speech: music training facilitates pitch processing in both music and language

The main aim of the present experiment was to determine whether extensive musical training facilitates pitch contour processing not only in music but also in language. We used a parametric manipulation of final notes' or words' fundamental frequency (F0), and we recorded behavioral and electrophysiological data to examine the precise time course of pitch processing. We compared professional musicians and nonmusicians. Results revealed that within both domains, musicians detected weak F0 manipulations better than nonmusicians. Moreover, F0 manipulations within both music and language elicited similar variations in brain electrical potentials, with overall shorter onset latency for musicians than for nonmusicians. Finally, the scalp distribution of an early negativity in the linguistic task varied with musical expertise, being largest over temporal sites bilaterally for musicians and largest centrally and over left temporal sites for nonmusicians. These results are taken as evidence that extensive musical training influences the perception of pitch contour in spoken language.     

Mechanisms of neuronal hyperexcitability caused by partial inhibition of Na+-K+-ATPases in the rat CA1 hippocampal region

Extra- and intracellular records were made from rat acute hippocampal slices to examine the effects of partial inhibition of Na(+)-K(+)-ATPases (Na(+)-K(+) pumps) on neuronal hyperexcitability. Bath application of the low-affinity cardiac glycoside, dihydroouabain (DHO), reversibly induced interictal-like epileptiform bursting activity in the CA1 region. Burst-firing was correlated with inhibition of the pumps, which was assayed by changes in [K(+)](o) uptake rates measured with K(+)-ion-sensitive microelectrodes. Large increases in resting [K(+)](o) did not occur. DHO induced a transient depolarization (5-6 mV) followed by a long-lasting hyperpolarization (approximately 6 mV) in CA1 pyramidal neurons, which was accompanied by a 30% decrease in resting input resistance. Block of an electrogenic pump current could explain the depolarization but not the hyperpolarization of the membrane. Increasing [K(+)](o) from 3 to 5.5 mM minimized these transient shifts in passive membrane properties without preventing DHO-induced hyperexcitability. DHO decreased synaptic transmission, but increased the coupling between excitatory postsynaptic potentials and spike firing (E-S coupling). Monosynaptic inhibitory postsynaptic potential (IPSP) amplitudes declined to approximately 25% of control at the peak of bursting activity; however, miniature TTX-resistant inhibitory postsynaptic current amplitudes were unaffected. DHO also reduced the initial slope of the intracellular excitatory postsynaptic potential (EPSP) to approximately 40% of control. The conductances of pharmacologically isolated IPSPs and EPSPs in high-Ca/high-Mg-containing saline were also reduced by DHO by approximately 50%. The extracellular fiber volley amplitude was reduced by 15-20%, suggesting that the decrease in neurotransmission was partly due to a reduction in presynaptic fiber excitability. DHO enhanced a late depolarizing potential that was superimposed on the EPSP and could obscure it. This potential was not blocked by antagonists of NMDA receptors, and blockade of NMDA, mGlu, or GABA(A) receptors did not affect burst firing. The late depolarizing component enabled the pyramidal cells to reach spike threshold without changing the actual voltage threshold for firing. We conclude that reduced GABAergic potentials and enhanced E-S coupling are the primary mechanisms underlying the hyperexcitability associated with impaired Na(+)-K(+) pump activity.     

An unusual intraventricular interthalamic vein: two anatomical case reports

Neurosurgeons use ventricular veins during an endoscopic third ventriculocisternostomy as landmark to progress in ventricles. In the current literature, there is lack of detailed intraventricular venous anatomy. Majority of those papers treats Monro’s foramen venous variations. There are no data of third ventricle venous anatomy and variations in the literature. We reported two cases of unusual interthalamic vein that we need to spare during endoscopy.     

Molecular mechanism of systemic delivery of neural precursor cells to the brain: assembly of brain endothelial apical cups and control of transmigration by CD44

Systemically injected neural precursor cells (NPCs) were unexpectedly shown to reach the cerebral parenchyma and induce recovery in various diffuse brain pathologies, including animal models of multiple sclerosis. However, the molecular mechanisms supporting NPC migration across brain endothelium remain elusive. Brain endothelium constitutes the blood-brain barrier, which uniquely controls the access of drugs and trafficking of cells, including leukocytes, from the blood to the brain. Taking advantage of the availability of in vitro models of human and rat blood-brain barrier developed in our laboratory and validated by us and others, we show here that soluble hyaluronic acid, the major ligand of the adhesion molecule CD44, as well as anti-CD44 blocking antibodies, largely prevents NPC adhesion to and migration across brain endothelium in inflammatory conditions. We present further evidence that NPCs, surprisingly, induce the formation of apical cups at the surface of brain endothelial cells, enriched in CD44 and other adhesion molecules, thus hijacking the endothelial signaling recently shown to be involved in leukocyte extravasation. These results demonstrate the pivotal role of CD44 in the trans-endothelial migration of NPCs across brain endothelial cells: we propose that they may help design new strategies for the delivery of therapeutic NPCs to the brain by systemic administration.     

A Process for Polymerizing Vinyl Phosphonic Acid with C6F13I Perfluoroalkyl Iodide Chain‐Transfer Agent

The synthesis of oligomeric VPA structures via the CTA perfluorohexyl iodide has been investigated. NMR and MALDI‐TOF MS analysis showed that the structures were produced exclusively by radical‐transfer reactions. The oligomers had a molecular weight above 2 000 g · mol⁻¹ and exhibited intra‐ and intermolecular anhydrous bonding. The investigation showed that the reaction is not a living (controlled) system, but follows conventional radical telomerization. The value for the transfer constant for C₆F₁₃I to VPA was found to be 3.4 at 70 °C and 4.3 at 80 °C. This high value may be partially explained by a low k/k_t ratio, which suggests a low k_p. The oligomeric structures showed a relatively high resistance to thermal degradation.

     

Obstetric competence among primary healthcare workers in Mali

Objective

To determine individual and contextual factors associated with emergency obstetric and neonatal care (EmONC) competency among primary healthcare staff in Mali.

Methods

Between November 2011 and April 2012, a competency test was administered to 196 healthcare workers in 65 community health centers in Mali. The test was scored from 0 to 100, and differences among 5 areas of EmONC were assessed. A multilevel linear regression model was used to determine individual and contextual factors associated with score.

Results

The mean score was 66.7 (minimum, 15.9; maximum, 97.7). Knowledge was most deficient for postpartum infection and hypertensive complications. Type of health worker, years of experience, number of days absent, and availability of guidelines for management of obstetric complications within the health center were positively associated with test score (P < 0.05). Availability of guidelines was associated with higher competency of physicians, health technicians, and obstetric nurses (P < 0.001), and seemed to influence the competency of healthcare workers with fewer than 10 years of experience in particular.

Conclusion

Guidelines must be developed that will facilitate standardization of the management of postpartum infection and other less common complications for which healthcare workers show low competence. Strategies to increase use of these guidelines will be necessary.