Noninvasive Brain Stimulation and Noninvasive Peripheral Stimulation for Neglect Syndrome Following Acquired Brain Injury

OBJECTIVE: Hemispatial neglect is a frequent condition usually following nondominant hemispheric brain injury. It strongly affects rehabilitation strategies and everyday life activities. It is associated with behavioral and cognitive disability with a strong impact on patient's life. METHODS: We reviewed the published literature on the use of noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), and of noninvasive peripheral muscle stimulation, as therapeutic strategies for rehabilitation of neglect after acquired brain injury, such as in stroke or in traumatic injuries. The studies were grouped as controlled or uncontrolled studies in each stimulation techniques. RESULTS: Thirty-four studies were identified and 16 on rTMS, 10 on tDCS, and 8 on vibration. All studies were conducted in adult patients who suffered a stroke, except for one that was conducted in a patient suffering traumatic acquired brain injury and another that was conducted in a patient with brain tumor. In spite of significant variability in treatment protocols, patients' features and assessment of neglect, improvement was reported in almost all studies with no side-effects. CONCLUSIONS: Noninvasive brain stimulation and neuromuscular vibration are promising therapeutic neuromodulatory approaches for neglect. Further randomized-controlled studies are needed to corroborate their effectiveness as separate and combined techniques

Critical behavior of density of states near Fermi energy in low-dimensional disordered metals

We study the effect of electron-electron interaction on the one-particle density of states (\emph{DOS}) $\rho^{(d)}(\epsilon,T)$ of low-dimensional disordered metals near Fermi energy within the framework of the finite temperature conventional impurity diagram technique. We consider only diffusive limit and by a geometric re-summation of the most singular first order self-energy corrections via the Dyson equation we obtain a non-divergent solution for the \emph{DOS} at low energies, while for higher energies the well-known Altshuler-Aronov corrections are recovered. At the Fermi level $\rho^{(d)}(\epsilon,T=0)\to 0$, this indicates that interacting disordered two- and quasi-one-dimensional systems are in insulating state at zero temperature. The obtained results are in good agreement with recent tunneling experiments on two-dimensional GaAs/AlGaAs heterostructures and quasi-one-dimensional doped multiwall carbon nanotubes.Comment: 8 pages, 4 figure

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation

OBJECTIVE: Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. METHODS: Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. RESULTS: Magnetic-PAS, but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. CONCLUSION: Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. SIGNIFICANCE: Application of magnetic-PAS might be relevant for motor rehabilitation

Effect of Substitutional Impurities on the Electronic States and Conductivity of Crystals with Half-filled Band

Low temperature quantum corrections to the density of states (DOS) and the conductivity are examined for a two-dimensional(2D) square crystal with substitutional impurities. By summing the leading logarithmic corrections to the DOS its energy dependence near half-filling is obtained. It is shown that substitutional impurities do not suppress the van Hove singularity at the middle of the band, however they change its energy dependence strongly. Weak disorder due to substitutional impurities in the three-dimensional simple cubic lattice results in a shallow dip in the center of the band. The calculation of quantum corrections to the conductivity of a 2D lattice shows that the well-known logarithmic localization correction exists for all band fillings. Furthermore the magnitude of the correction increases as half-filling is approached. The evaluation of the obtained analytical results shows evidence for delocalized states in the center of the band of a 2D lattice with substitutional impurities

Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants.

Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. Susceptibility to gastric digestion was assessed in an in vitro model. Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. SIgA1 assembly appeared superior to SIgA2 in plants. Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68-61 SIgA1. The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs

Teager–Kaiser energy operator signal conditioning improves EMG onset detection

Accurate identification of the onset of muscle activity is an important element in the biomechanical analysis of human movement. The purpose of this study was to determine if inclusion of the Teager–Kaiser energy operator (TKEO) in signal conditioning would increase the accuracy of popular electromyography (EMG) onset detection methods. Three methods, visual determination, threshold-based method, and approximated generalized likelihood ratio were used to estimate the onset of EMG burst with and without TKEO conditioning. Reference signals, with known onset times, were constructed from EMG signals collected during isometric contraction of the vastus lateralis (n = 17). Additionally, vastus lateralis EMG signals (n = 255) recorded during gait were used to evaluate a clinical application of the TKEO conditioning. Inclusion of TKEO in signal conditioning significantly reduced mean detection error of all three methods compared with signal conditioning without TKEO, using artificially generated reference data (13 vs. 98 ms, p < 0.001) and also compared with experimental data collected during gait (55 vs. 124 ms, p < 0.001). In conclusion, addition of TKEO as a step in conditioning surface EMG signals increases the detection accuracy of EMG burst boundaries

SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses

Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-19F-NMR

The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using 19F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane

Weaning practices in phenylketonuria vary between health professionals in Europe

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe