Electrical Vestibular Stimulation after Vestibular Deafferentation and in Vestibular Schwannoma

Background

Vestibular reflexes, evoked by human electrical (galvanic) vestibular stimulation (EVS), are utilized to assess vestibular function and investigate its pathways. Our study aimed to investigate the electrically-evoked vestibulo-ocular reflex (eVOR) output after bilateral and unilateral vestibular deafferentations to determine the characteristics for interpreting unilateral lesions such as vestibular schwannomas.

Methods

EVOR was recorded with dual-search coils as binocular three-dimensional eye movements evoked by bipolar 100 ms-step at EVS intensities of [0.9, 2.5, 5.0, 7.5, 10.0]mA and unipolar 100 ms-step at 5 mA EVS intensity. Five bilateral vestibular deafferented (BVD), 12 unilateral vestibular deafferented (UVD), four unilateral vestibular schwannoma (UVS) patients and 17 healthy subjects were tested with bipolar EVS, and five UVDs with unipolar EVS.

Results

After BVD, bipolar EVS elicited no eVOR. After UVD, bipolar EVS of one functioning ear elicited bidirectional, excitatory eVOR to cathodal EVS with 9 ms latency and inhibitory eVOR to anodal EVS, opposite in direction, at half the amplitude with 12 ms latency, exhibiting an excitatory-inhibitory asymmetry. The eVOR patterns from UVS were consistent with responses from UVD confirming the vestibular loss on the lesion side. Unexpectedly, unipolar EVS of the UVD ear, instead of absent response, evoked one-third the bipolar eVOR while unipolar EVS of the functioning ear evoked half the bipolar response.

Conclusions

The bidirectional eVOR evoked by bipolar EVS from UVD with an excitatory-inhibitory asymmetry and the 3 ms latency difference between normal and lesion side may be useful for detecting vestibular lesions such as UVS. We suggest that current spread could account for the small eVOR to 5 mA unipolar EVS of the UVD ear.     

Diagnosing Developmental Dyscalculia on the Basis of Reliable Single Case FMRI Methods: Promises and Limitations

FMRI-studies are mostly based on a group study approach, either analyzing one group or comparing multiple groups, or on approaches that correlate brain activation with clinically relevant criteria or behavioral measures. In this study we investigate the potential of fMRI-techniques focusing on individual differences in brain activation within a test-retest reliability context. We employ a single-case analysis approach, which contrasts dyscalculic children with a control group of typically developing children. In a second step, a support-vector machine analysis and cluster analysis techniques served to investigate similarities in multivariate brain activation patterns. Children were confronted with a non-symbolic number comparison and a non-symbolic exact calculation task during fMRI acquisition. Conventional second level group comparison analysis only showed small differences around the angular gyrus bilaterally and the left parieto-occipital sulcus. Analyses based on single-case statistical procedures revealed that developmental dyscalculia is characterized by individual differences predominantly in visual processing areas. Dyscalculic children seemed to compensate for relative under-activation in the primary visual cortex through an upregulation in higher visual areas. However, overlap in deviant activation was low for the dyscalculic children, indicating that developmental dyscalculia is a disorder characterized by heterogeneous brain activation differences. Using support vector machine analysis and cluster analysis, we tried to group dyscalculic and typically developing children according to brain activation. Fronto-parietal systems seem to qualify for a distinction between the two groups. However, this was only effective when reliable brain activations of both tasks were employed simultaneously. Results suggest that deficits in number representation in the visual-parietal cortex get compensated for through finger related aspects of number representation in fronto-parietal cortex. We conclude that dyscalculic children show large individual differences in brain activation patterns. Nonetheless, the majority of dyscalculic children can be differentiated from controls employing brain activation patterns when appropriate methods are used.     

TGFβs Modulate Permeability of the Blood-Epididymis Barrier in an In Vitro Model

The blood-epididymis barrier (BEB) is formed by epithelial tight junctions mediating selective permeability of the epididymal epithelium. Defective barrier function can disturb the balance of the epididymal milieu, which may result in infertility. The stroma of the epididymis contains high amounts of cytokines of the TGFβ family of unknown function. We screened possible effects of all three TGFβ isoforms on paracellular tightness in a BEB in vitro model based on the strongly polarized mouse epididymal epithelial MEPC5 cells in the transwell system. In this model we found a robust transepithelial electrical resistance (TER) of about 840 Ω x cm². Effects on the paracellular permeability were evaluated by two methods, TER and FITC-Dextran-based tracer diffusion assays. Both assays add up to corresponding results indicating a time-dependent disturbance of the BEB differentially for the three TGFβ isoforms (TGFβ3>TGFβ1>TGFβ2) in a TGFβ-recetor-1 kinase- and Smad-dependent manner. The tight junction protein claudin-1 was found to be reduced by the treatment with TGFβs, whereas occludin was not influenced. Epididymal epithelial cells are predominantly responsive to TGFβs from the basolateral side, suggesting that TGFβ may have an impact on the epididymal epithelium from the stroma in vivo. Our data show for the first time that TGFβs decrease paracellular tightness in epididymal epithelial cells, thus establishing a novel mechanism of regulation of BEB permeability, which is elementary for sperm maturation and male fertility.     

Quantitative Changes in the Sleep EEG at Moderate Altitude (1630 m and 2590 m)

Background

Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep.

Methods

Fourty-four healthy men (mean age 25.0±5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design.

Results

Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8–4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (∼4% at 1630 m and 15% at 2590 m), while theta activity (4.6–8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4–8 Hz and 13–14.4 Hz) and breathing variables (AHI, ODI; 0.8–4.6 Hz).

Conclusions

The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.     

Gaze Holding in Healthy Subjects

Eccentric gaze in darkness evokes minor centripetal eye drifts in healthy subjects, as cerebellar control sufficiently compensates for the inherent deficiencies of the brainstem gaze-holding network. This behavior is commonly described using a leaky integrator model, which assumes that eye velocity grows linearly with gaze eccentricity. Results from previous studies in patients and healthy subjects suggest caution when this assumption is applied to eye eccentricities larger than 20 degrees. To obtain a detailed characterization of the centripetal gaze-evoked drift, we recorded horizontal eye position in 20 healthy subjects. With their head fixed, they were asked to fixate a flashing dot (50 ms every 2 s)that was quasi-stationary displacing(0.5 deg/s) between ±40 deg horizontally in otherwise complete darkness. Drift velocity was weak at all angles tested. Linearity was assessed by dividing the range of gaze eccentricity in four bins of 20 deg each, and comparing the slopes of a linear function fitted to the horizontal velocity in each bin. The slopes of single subjects for gaze eccentricities of ±0−20 deg were, in median,0.41 times the slopes obtained for gaze eccentricities of ±20−40 deg. By smoothing the individual subjects'' eye velocity as a function of gaze eccentricity, we derived a population of position-velocity curves. We show that a tangent function provides a better fit to the mean of these curves when large eccentricities are considered. This implies that the quasi-linear behavior within the typical ocular motor range is the result of a tuning procedure, which is optimized in the most commonly used range of gaze. We hypothesize that the observed non-linearity at eccentric gaze results from a saturation of the input that each neuron in the integrating network receives from the others. As a consequence, gaze-holding performance declines more rapidly at large eccentricities.     

A Real-Time PCR Assay for the Detection of Atypical Strains of Chlamydiaceae from Pigeons

Recent evidence of the occurrence of atypical Chlamydiaceae strains in pigeons, different from the established Chlamydiaceae, requires the development of a specific and rapid detection tool to investigate their prevalence and significance. Here is described a new real-time PCR assay that allows specific detection of atypical Chlamydiaceae from pigeons. The assay has been used to assess the dissemination of these strains in field samples collected from Parisian pigeon populations in 2009. The results suggest a limited dissemination compared to the usually higher prevalence of Chlamydia psittaci that is the main species associated with avian chlamydiosis.     

Effects of Acute Exposure to Moderate Altitude on Vascular Function,Metabolism and Systemic Inflammation

Background

Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown.

Objectives

To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

Methods

In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported.

Results

Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m.

Conclusions

Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01130948","term_id":"NCT01130948"}}NCT01130948     

Alterations in miRNA Levels in the Dentate Gyrus in Epileptic Rats

The aim of this study was to characterize changes in miRNA expression in the epileptic dentate gyrus. Status epilepticus evoked by amygdala stimulation was used to induce epilepsy in rats. The dentate gyri were isolated at 7 d, 14 d, 30 d and 90 d after stimulation (n=5). Sham-operated time-matched controls were prepared for each time point (n=5). The miRNA expression was evaluated using Exiqon microarrays. Additionally, mRNA from the same animals was profiled using Affymetrix microarrays. We detected miRNA expression signatures that differentiate between control and epileptic animals. Significant changes in miRNA expression between stimulated and sham operated animals were observed at 7 and 30 d following stimulation. Moreover, we found that there are ensembles of miRNAs that change expression levels over time. Analysis of the mRNA expression from the same animals revealed that the expression of several mRNAs that are potential targets for miRNA with altered expression level is regulated in the expected direction. The functional characterization of miRNAs and their potential mRNA targets indicate that miRNA can participate in several molecular events that occur in epileptic tissue, including immune response and neuronal plasticity. This is the first report on changes in the expression of miRNA and the potential functional impact of these changes in the dentate gyrus of epileptic animals. Complex changes in the expression of miRNAs suggest an important role for miRNA in the molecular mechanisms of epilepsy.     

Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

The influence of phylogeny and ecology on root,shoot and plant ionomes of 14 native Brazilian species

The ionome is the elemental composition of a living organism, its tissues, cells or cell compartments. The ionomes of roots, stems and leaves of 14 native Brazilian forest species were characterised to examine the relationships between plant and organ ionomes and the phylogenetic and ecological affiliations of species. The null hypothesis that ionomes of Brazilian forest species and their organs do not differ was tested. Concentrations of mineral nutrients in roots, stems and leaves were determined for 14 Brazilian forest species, representing seven angiosperm orders, grown hydroponically in a complete nutrient solution. The 14 species could be differentiated by their ionomes and the partitioning of mineral nutrients between organs. The ionomic differences between the 14 species did not reflect their phylogenetic relationships or successional ecology. Differences between shoot ionomes and root ionomes were greater than differences in the ionome of an organ when compared among genotypes. In conclusion, differences in ionomes of species and their organs reflect a combination of ancient phylogenetic and recent environmental adaptations.