Isometric agonist and antagonist muscle activation interacts differently with 140-Hz transcranial alternating current stimulation aftereffects at different intensities.

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca2+ increase, and their role in the aftereffects of tACS.NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.

Morphology--composition correlations in carbon nanotubes synthesised with nitrogen and phosphorus containing precursors.

We have correlated the elemental composition with the structure of multi-wall carbon nanotubes synthesised with nitrogen and phosphorus containing precursors and identified two chemically distinct dominant morphologies. The first type are cone-structured tubes and the second are nanotubes with fewer walls which can accommodate N2 gas along their inner channel and contain up to ten times more nitrogen than the cone-structured nanotubes. Phosphorus was present in the catalyst particles but was not detected within the walls of either type of nanotube. Elemental analysis combined with in situ electrical measurements has allowed us to monitor the evolution of the doped nanotubes when current is passed. The N2 gas becomes bonded immediately when current flows and the gas-containing nanotubes restructure more easily than the cone-structured ones. Since the inclusion of heteroatoms in multi-wall carbon nanotubes is generally inhomogeneous, understanding the distribution of elements across the sample is an important step towards the optimization of devices including gas sensors and components in electrical applications.

Brain-derived neurotrophic factor: its impact upon neuroplasticity and neuroplasticity inducing transcranial brain stimulation protocols.

Val66Met (rs6265) is a gene variation, a single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene that codes for the protein BDNF. The substitution of Met for Val occurs at position 66 in the pro-region of the BDNF gene and is responsible for altered activity-dependent release and recruitment of BDNF in neurons. This is believed to manifest itself in an altered ability in neuroplasticity induction and an increased predisposition toward a number of neurological disorders. Many studies using neuroplasticity-inducing protocols have investigated the impact of the BDNF polymorphism on cortical modulation and plasticity; however, the results are partly contradictory and dependent on the paradigm used in a given study. The aim of this review is to summarize recent knowledge on the relationship of this BDNF SNP and neuroplasticity.

Immunological and molecular targets of atopic dermatitis treatment.

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with a highly variable clinical phenotype and heterogeneous pathophysiology. Its pathogenesis is associated with alterations to both the skin barrier and the immune system, which may in turn be influenced by genetic mutations and the patient's environment. Basic and translational research, as well as clinical trials, have helped broaden our knowledge of the molecular mechanisms underlying the development of AD and to identify potential treatment targets and approaches. These include new ways of reducing transepidermal water loss and the shedding of corneocytes, new ways of interacting with established molecular targets (such as histamine receptors and interleukins and other T-cell cytokines), and the identification of new molecular targets (such as toll-like receptors and tight junction proteins). Well-established treatment options such as emollients, corticosteroids and topical calcineurin inhibitors will clearly continue to have a role in treating AD. Among the new agents that could be joining them in the near future are sphinganin (a precursor of ceramides 1 and 3), cannabinoids, highly targeted monoclonal antibodies and subcutaneous immunotherapy.

Spin-stretching modes in anisotropic magnets: spin-wave excitations in the multiferroic Ba2CoGe2O7.

We studied spin excitations in the magnetically ordered phase of the noncentrosymmetric Ba(2)CoGe(2)O(7) in high magnetic fields up to 33 T. In the electron spin resonance and far infrared absorption spectra we found several spin excitations beyond the two conventional magnon modes expected for such a two-sublattice antiferromagnet. We show that a multiboson spin-wave theory describes these unconventional modes, including spin-stretching modes, characterized by an oscillating magnetic dipole and quadrupole moment. The lack of inversion symmetry allows each mode to become electric dipole active. We expect that the spin-stretching modes can be generally observed in inelastic neutron scattering and light absorption experiments in a broad class of ordered S > 1/2 spin systems with strong single-ion anisotropy and/or noncentrosymmetric lattice structure.

Evaluating Current Density Modeling of Non-Invasive Eye and Brain Electrical Stimulation Using Phosphene Thresholds.

Because current flow cannot be measured directly in the intact retina or brain, current density distribution models were developed to estimate it during magnetic or electrical stimulation. A paradigm is now needed to evaluate if current flow modeling can be related to physiologically meaningful signs of true current distribution in the human brain. We used phosphene threshold measurements (PTs) as surrogate markers of current-flow to determine if PTs, evoked by transcranial alternating current stimulation (tACS), can be matched with current density estimates generated by head model-based computer simulations. Healthy, male subjects (n=15) were subjected to three-staged PT measurements comparing six unilateral and one bilateral stimulation electrode montages according to the 10/20 system: Fp2-Suborbital right (So), Fp2-right shoulder (rS), Fp2-Cz, Fp2- O2, So-rS, Cz-F8 and F7-F8. The stimulation frequency was set at 16 Hz. Subjects were asked to report the appearance and localization of phosphenes in their visual field for every montage. Current density models were built using multi-modal imaging data of a standard brain, meshed with isotropic conductivities of different tissues of the head using the SimBio and SCIRun software packages. We observed that lower PTs were associated with higher simulated current levels in the unilateral montages of the model head, and shorter electrode distances to the eye had lower PTs. The lowest mean PT and the lowest variability were found in the F7-F8 montage ( [Formula: see text]). Our results confirm the hypothesis that phosphenes are primarily of retinal origin, and they provide the first in vivo evidence that computer models of current flow using head models are a valid tool to estimate real current flow in the human eye and brain.

Respiratory distress after surgery of RVOT pathologies: a word of caution on pseudoaneurysm development.

Pseudoaneurysm of the right ventricle outflow tract (RVOT) is a rare complication in pediatric cardiac surgery. We report a patient who developed a right ventricular pseudoaneurysm 8 months after RVOT enlargement using a pericardial patch for infundibular pulmonary stenosis. Our patient was born with severe pulmonary valvular stenosis and treated with percutaneous balloon valvotomy in the neonatal period. Six months later, she developed infundibular pulmonary stenosis, which required surgical resection of right ventricle infundibular trabeculations and bovine pericardial patch enlargement. The postoperative period was normal. She was readmitted to hospital 5 months later complaining of wheezing, coughing and shortness of breath. Echocardiography showed a huge aneurysmal dilatation of the outflow patch in connection with the right ventricular cavity. The patient underwent resection of the pseudoaneurysm and former patch, followed by interposition of a bovine jugular vein conduit between the RVOT and pulmonary bifurcation. The early postoperative period was uncomplicated. On echocardiography, no significant residual gradient was measured through the conduit and there was no insufficiency of the valve. RVOT reconstruction with patch enlargement, homograft or conduit implantation can be the origin of pseudoaneurysms. Although their incidence is rare, they are often asymptomatic before becoming quite large and causing compression symptoms as in our patient with respiratory complaints due to airway compression. It is important to follow up these patients closely, especially in the first year after surgery since most aneurysms develop within 6 months of surgery.

[Transcranial magnetic and direct current stimulation in the therapy of pain]. / Transkranielle repetitive Magnet- und Gleichstromstimulation in der Schmerztherapie.

Neuroplasticity is the ability of the central nervous system to induce functional and microstructural changes in order to adapt to a new environment. However, so-called maladaptive neuroplasticity can also bring disadvantages, such as reduced inhibition of input signals, one of the suspected causes of chronic pain. With the method of repetitive transcranial magnetic stimulation (rTMS) a technique has been developed that makes it possible to study cortical excitability changes in the human brain non-invasively over a long time. Electrophysiological studies have shown that the application of rTMS over the primary motor cortex induces a facilitatory or inhibitory effect on the corticospinal and cortico-cortical excitability depending on the protocol used. The results of the clinical studies published suggest that rTMS can inhibit pain perception with regard to chronic pain and in experimentally induced pain conditions. An alternative method to induce neuroplastic changes is transcranial direct current stimulation (tDCS). tDCS acts primarily on the membrane potential, by hyper- or depolarizing it. The induced after-effects are NMDA receptor dependent. The effectiveness of tDCS is currently being explored in migraine research as well as experimentally induced and chronic pain conditions. In phase II trials its efficacy has been demonstrated. Ongoing studies are focusing on management of the placebo effect; however, it is easier to control this effect in tDCS compared to rTMS. Phase III trials are currently in preparation.

Personality and stress influence vision restoration and recovery in glaucoma and optic neuropathy following alternating current stimulation: implications for personalized neuromodulation and rehabilitation.

PURPOSE: Identifying factors that affect recovery or restoration of neurological function is a key goal of rehabilitation in neurology and ophthalmology. One such factor can be prolonged mental stress, which may be not only the consequence of nervous system damage but also a major risk factor, or cause, of neural inactivation. Using the visual system as a model of neural injury, we wished to study how patients' stress and personality profiles correlate with vision recovery as induced by therapy with alternating current stimulation (ACS) in patients with optic nerve damage. METHODS: Personality and stress questionnaires were sent retrospectively to a clinical convenience sample of patients who suffer low vision due to optic nerve damage, which had previously been treated with ACS. The questionnaires included the NEO Five-Factor Inventory (NEO-FFI), the Trier Inventory of Chronic Stress (TICS), and the Flammer syndrome (FS) checklist, which probes signs of vascular dysregulation (VD). These scores were then correlated with the extent of ACS-induced vision restoration as recorded 1-3 years earlier by perimetric visual field tests. RESULTS: Two NEO-FFI personality factors (lower neuroticism, higher conscientiousness) and the presence of physiological Flammer signs were associated with greater recovery as were individual items of the factors openness and agreeableness. Single NEO-FFI item analysis revealed that recovery relates to greater extraversion (optimistic and happy), openness (less guided by authorities for decisions on moral issues), and agreeableness (argue less, like working with others, thoughtful, considerate) as well as the presence of FS signs (cold hands/feet, hypotension, slim body shapes, tinnitus). This suggests that patients with better recovery were more calm, peaceful and secure, hard-working, and reliable, and with high organizational skills. In contrast, patients with poor recovery had a tendency to be emotionally unstable, anxious, unhappy and prone to negative emotions, impulsive, careless, and unorganized. Chronic stress assessed with TICS did not correlate with recovery. CONCLUSION: Vision restoration induced by ACS is greater in patients with less stress-prone personality traits and those who show signs of VD. Prospective studies are now needed to determine if personality has (i) a causal influence, i.e., patients with less stress-prone personalities and greater VD signs recover better, and/or (ii) if personality changes are an effect of the treatment, i.e., successful recovery induces personality changes. Though the cause-effect relationship is still open, we nevertheless propose that psychosocial factors and VD contribute to the highly variable outcome of vision restoration treatments in low vision rehabilitation. This has implications for preventive and personalized vision restoration and is of general value for our understanding of outcome variability in neuromodulation and neurological rehabilitation.

Does the menstrual cycle influence the motor and phosphene thresholds in migraine?

BACKGROUND AND PURPOSE: The excitability of the visual and motor cortical areas is altered in migraineurs. Controversial results of previous studies on cortical excitability may depend on the hormonal status of female subjects. The present study aimed to determine whether the different phases of the menstrual cycle influence the phosphene thresholds (PT) and resting motor thresholds (RMT) in migraineurs. METHODS: Thirty-two migraine patients participated in this study. Three to six PT and RMT measurements were done in headache-free intervals during the follicular, middle and luteal phases of the female cycle, or in active dosage and withdrawal phases in patients who were taking low dosage oral contraceptives. RESULTS: Generally, PTs showed higher individual variabilities than RMTs. Additionally, we have observed that the RMTs and PTs were significantly independent from hormonal changes. However, patients who were taking a low dosage of oral contraceptives had lower PTs compared with patients who were not taking oral contraceptives. RMTs show the opposite tendency. CONCLUSION: The results imply that PTs and RMTs can be reliably measured independently from the menstrual hormone status in female migraineurs.

Neurofibromatosis.

Neurofibromatosis (NF) is one of the most common genetic disorders. Inherited in an autosomal dominant fashion, this phacomatosis is classified into two genetically distinct subtypes characterized by multiple cutaneous lesions and tumors of the peripheral and central nervous system. Neurofibromatosis type 1 (NF1), also referred to as Recklinghausen's disease, affects about 1 in 3500 individuals and presents with a variety of characteristic abnormalities of the skin and the peripheral nervous system. Neurofibromatosis type 2 (NF2), previously termed central neurofibromatosis, is much more rare occurring in less than 1 in 25 000 individuals. Often first clinical signs of NF2 become apparent in the late teens with a sudden loss of hearing due to the development of bi- or unilateral vestibular schwannomas. In addition NF2 patients may suffer from further nervous tissue tumors such as meningiomas or gliomas. This review summarizes the characteristic features of the two forms of NF and outlines commonalities and distinctions between NF1 and NF2.

[Considerable variation in the range of time for complications to appear after tattoos]. / Erhebliche zeitliche Variationsbreite von Komplikationen nach Tätowierungen.

Side effects after tattoos are being observed with greater frequency in dermatological practice. The complications that occur can be classified into systemic and local reactions. The time course of cutaneous side effects ranges from direct complications during or following tattooing to reactions that first appear several years thereafter. The majority of allergic complications can be explained by the delayed degradation of the color pigment used for the tattoo and then release of potent allergens sometimes not until years later.

Dynamic strain in gold nanoparticle supported graphene induced by focused laser irradiation.

Graphene on noble-metal nanostructures constitutes an attractive nanocomposite with possible applications in sensors or energy conversion. In this work we study the properties of hybrid graphene/gold nanoparticle structures by Raman spectroscopy and scanning probe methods. The nanoparticles (NPs) were prepared by local annealing of gold thin films using a focused laser beam. The method resulted in a patterned surface, with NPs formed at arbitrarily chosen microscale areas. Graphene grown by chemical vapour deposition was transferred onto the prepared, closely spaced gold NPs. While we found that successive higher intensity (6 mW) laser irradiation increased gradually the doping and the defect concentration in SiO2 supported graphene, the same irradiation procedure did not induce such irreversible effects in the graphene supported by gold NPs. Moreover, the laser irradiation induced a dynamic hydrostatic strain in the graphene on Au NPs, which turned out to be completely reversible. These results can have implications in the development of graphene/plasmonic nanoparticle based high temperature sensors operating in dynamic regimes.

P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic relaxation of the human colon in vitro.

Neurotransmitters released by myenteric neurons regulate movements of intestinal smooth muscles. There has been little pharmacological evidence for a role of purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of the human large intestine. We used P(2) purinoceptor antagonists to assess whether such receptors are involved in the NANC relaxation of the circular muscle of the human sigmoid colon. It was also investigated whether the guanylate cyclase enzyme mediates the NANC response. Human colonic circular strips were tested in organ bath experiments with isotonic recording. NANC, non-nitrergic relaxations induced by electrical field stimulation (1 and 10 Hz, in the presence of atropine, guanethidine, and 100 microM N(G)-nitro-L-arginine [L-NOARG]) were strongly inhibited by a combination of the P(2) purinoceptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-sulfonic acid (PPADS) (50 microM) and suramin (100 microM). PPADS plus suramin was ineffective in the absence of L-NOARG. L-NOARG alone significantly reduced the NANC relaxation to electrical stimulation. PPADS plus suramin strongly inhibited the relaxation in response to exogenous alpha,beta-methylene ATP. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 microM) inhibited the NANC relaxation, but did not add to its reduction by L-NOARG. L-NOARG was still slightly effective in the presence of ODQ. Vasoactive intestinal polypeptide tachyphylaxis failed to influence the non-nitrergic NANC relaxation. It is concluded that nitric oxide (NO) and ATP co-mediate, in a non-additive manner, the NANC relaxation. NO probably acts through the guanylate cyclase, though a small fraction of its effect might be mediated by other mechanisms. Activators of the guanylate cyclase other than NO do not seem to participate in the NANC relaxation.

Time dependent decomposition of ammonia borane for the controlled production of 2D hexagonal boron nitride.

Ammonia borane (AB) is among the most promising precursors for the large-scale synthesis of hexagonal boron nitride (h-BN) by chemical vapour deposition (CVD). Its non-toxic and non-flammable properties make AB particularly attractive for industry. AB decomposition under CVD conditions, however, is complex and hence has hindered tailored h-BN production and its exploitation. To overcome this challenge, we report in-depth decomposition studies of AB under industrially safe growth conditions. In situ mass spectrometry revealed a time and temperature-dependent release of a plethora of NxBy-containing species and, as a result, significant changes of the N:B ratio during h-BN synthesis. Such fluctuations strongly influence the formation and morphology of 2D h-BN. By means of in situ gas monitoring and regulating the precursor temperature over time we achieve uniform release of volatile chemical species over many hours for the first time, paving the way towards the controlled, industrially viable production of h-BN.

Publisher Correction: Time dependent decomposition of ammonia borane for the controlled production of 2D hexagonal boron nitride.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.