Stimulation Of Skin Research Articles

The influence of skin stimulation on the reach movement

The influence of skin stimulation on the reach movement

Cold evoked potentials: Acquisition from cervical dermatomes

Cold evoked potentials (CEPs) represent a novel technique to assess the integrity of cold-specific pathways within the somatosensory system. So far an objective assessment of these pathways has not been implemented into the clinical routine. Specifically, CEPs may help to elucidate the pathophysiological underpinnings of altered cold processing in neurological diseases. To test feasibility and test-retest reliability of CEPs within two cervical dermatomes, including recording sites in glabrous and hairy skin, in order to facilitate the transition into clinical practice. Twenty healthy subjects received 15 cold stimuli applied by a thermode either at the hand dorsum (C6 dermatome, hairy skin), the shoulder (C4 dermatome, hairy skin) or the thenar eminence (C6 dermatome, glabrous skin). Stimuli were applied from a baseline temperature of 30°C down to a destination temperature of 25°C at a rate of 20°C/s. N2 latencies and N2P2 amplitudes were recorded at the vertex using a surface electroencephalogram and test-retest statistics were calculated. Slight, innocuous cooling (Δ5°C) from a baseline temperature of 30°C elicited a brief percept of cooling and generated a vertex potential (N2P2) in most subjects. The latency of the vertex response is consistent with A-delta fiber activation. Based on test-retest analyses (i.e., intraclass correlation coefficients (ICCs) and Bland-Altman analyses) reliability is best within the C4 dermatome and for stimulation of hairy skin. ICCs display fair to substantial (ICCs from 0.51-0.81) reliability for amplitudes across all stimulation sites, possibly due to floor effects. CEPs latencies, however, were only poorly reliable (ICCs from -0.13 to 0.31). The acquisition of CEPs from cervical dermatomes is feasible. Since involvement of cold-specific pathways is relevant for several pathologies in clinical neurology, the application of CEPs may complement existing techniques like contact heat and laser stimulation in the assessment of peripheral and central nervous system disorders. Future studies employing different stimulation paradigms using faster cooling are warranted in order to improve the signal-to-noise ratio.

Paclitaxel formulation with stable sustained-release behavior and its biological safety evaluation

Biological safety and stable sustained-release of the drug are two crucial issues involved in the formulation of paclitaxel. Focusing on these issues, by using the FDA approved polylactide as carrier material, soybean lecithin as surfactant and maltodextrin as thickener, paclitaxel loaded PLA microspheres were simply prepared by solvent evaporation, thus guaranteeing the biological safety. The introduction of maltodextrin as a thickener aided to a stable sustained-release of paclitaxel. Surface morphology, particle size, drug loading rate, encapsulation efficiency and in vitro drug release behavior were investigated. Biological safety evaluations such as acute toxicity, allergies, hemolysis, skin stimulation and genotoxicity test were also carried out. Results showed that the obtained microspheres were biocompatible and could release paclitaxel at a desirable constant rate. Therefore, the simply prepared paclitaxel formulation with good biological safety and desirable release behavior exhibited great potential of local injection of paclitaxel for the clinical use in the future.

異常なfascia が原因と思われる運動器疼痛へ皮膚刺激ツール・ソマセプトミオを貼付した研究

異常なfascia が原因と思われる運動器疼痛へ皮膚刺激ツール・ソマセプトミオを貼付した研究

Trichogenic Photostimulation Using Monolithic Flexible Vertical AlGaInP Light-Emitting Diodes.

Alopecia is considered an aesthetic, psychological, and social issue among modern people. Although laser-induced skin stimulation is utilized for depilation treatment, such treatment has significant drawbacks of high energy consumption, huge equipment size, and limited usage in daily life. Here, we present a wearable photostimulator for hair-growth applications using high-performance flexible red vertical light-emitting diodes (f-VLEDs). Flexible microscale LEDs were effectively fabricated by a simple monolithic fabrication process, resulting in high light output (∼30 mW mm-2), low forward voltage (∼2.8 V), and excellent flexibility for wearable biostimulation. Finally, trichogenic stimulation of a hairless mouse was achieved using high-performance red f-VLEDs with high thermal stability, device uniformity, and mechanical durability.

Segmental innervation of the Göttingen minipig hind body. An electrophysiological study

The Göttingen minipig is being used increasingly in biomedical research. The anatomical structure of the porcine peripheral nervous system has been extensively characterized, but no equivalent to the dermatome map, which is so valuable in human neurophysiological research, has been created. We characterized the medullar segmental skin and muscle innervations of the minipig hind body, using neurophysiological methodology. Six adult minipigs underwent unilateral laminectomy from L2 to S3, exposing the nerve roots. The skin of the hind part of the body was divided into 36 predefined fields, based on anatomical landmarks for consistent reproducibility. We recorded the evoked potential in each exposed nerve root L2-S3 for cutaneous stimulation of each skin field, mapping the sensory innervation of the entire hind body. We subsequently recorded the motor response in seven predefined muscles during sequential stimulation of the L2-S3 nerve roots. We obtained a clear sensory evoked potential in the nerve roots during stimulation of the skin fields, allowing us to map the sensory innervation of the minipig hind body. Neurophysiological data from skin stimulation and muscle recordings enabled us to map the sensory innervation of the Göttingen minipig hind body and provide information about muscular innervation. The skin fields were sensory innervated by more than one root. The muscles each had one dominant root with minor contribution from neighboring roots. This is consistent with experimental data from human studies.

Non-leaching bactericidal cotton fabrics with well-preserved physical properties, no skin irritation and no toxicity

We developed an isocyanate group containing quaternary ammonium salt (IQAS) as a potential antimicrobial finishing agent that can be stored in a high purity form for more than a year in dry environments to permit convenient transportation and storage. Additionally, we report a facile and eco-friendly finishing technique to fabricate durable antimicrobial cotton fabrics using IQAS as an antimicrobial finishing agent by a dipping–padding–drying process. IQAS was bound onto the surface of cotton fabrics by a covalent bond to obtain a cotton fabric with excellent bactericidal activity, tearing strength, breaking elongation, bending rigidity, water vapor permeability, surface roughness and smoothness. The antimicrobial rates of these fabrics reached 92.2% and 98.5% against gram-negative bacterium Escherichia coli and gram-positive bacterium Staphylococcus aureus, respectively, even after 50 laundering cycles. These values are much higher than the reference antimicrobial rates of AAA class antimicrobial fabrics, as well as those of conventionally finished cotton fabrics, indicating that the IQAS finished cotton fabrics maintained excellent antimicrobial activity even after long-term repeated launderings. Moreover, the results indicate that the IQAS-treated cotton fabrics could improve the breaking strength (increased by 13.5% in the warp direction and 20.3% in the weft direction), the bursting strength (increased by 11.9%), the air permeability (increased by 12.6%) and the hydrophilicity compared to untreated cotton fabrics. Additionally, our non-leaching antimicrobial cotton fabrics treated with IQAS were non-toxic and showed no skin stimulation. Therefore, IQAS and the antimicrobial finishing technique reported here have great potential applications in antimicrobial fabrics used in hospitals, hotels and other susceptible situations. An isocyanate group containing quaternary ammonium salt that permits convenient transportation and storage was developed as a potential antimicrobial finishing agent to fabricate excellent antimicrobial cotton fabrics with well-preserved physical properties and security using a dipping–padding–drying process.

Amphibian (Xenopus laevis) Tadpoles and Adult Frogs Differ in Their Use of Expanded Repertoires of Type I and Type III Interferon Cytokines.

While amphibians around the globe are facing catastrophic declines, in part because of infections with pathogens such as the Frog Virus 3 (FV3) ranavirus; the mechanisms governing amphibian susceptibility and resistance to such pathogens remain poorly understood. The type I and type III interferon (IFN) cytokines represent a cornerstone of vertebrate antiviral immunity, while our recent work indicates that tadpoles and adult frogs of the amphibian Xenopus laevis may differ in their IFN responses to FV3. In this respect, it is notable that anuran (frogs and toads) tadpoles are significantly more susceptible to FV3 than adult frogs, and thus, gaining greater insight into the differences in the tadpole and adult frog antiviral immunity would be invaluable. Accordingly, we examined the FV3-elicited expression of a panel of type I and type III IFN genes in the skin (site of FV3 infection) and kidney (principal FV3 target) tissues and isolated cells of X. laevis tadpoles and adult frogs. We also examined the consequence of tadpole and adult frog skin and kidney cell stimulation with hallmark pathogen-associated molecular patterns (PAMPs) on the IFN responses of these cells. Together, our findings indicate that tadpoles and adult frogs mount drastically distinct IFN responses to FV3 as well as to viral and non-viral PAMPs, while these expression differences do not appear to be the result of a distinct pattern recognition receptor expression by tadpoles and adults.

Hyperdilution of CaHA fillers for the improvement of age and hereditary volume deficits in East Asian patients.

With their high elasticity and viscosity, calcium hydroxylapatite (CaHA) fillers are now widely used to treat age-related or hereditary facial soft tissue volume deficits. CaHA filler volume augmentation is further enhanced by its ability to stimulate neocollagenesis and improve skin quality. However, its high viscosity and cohesivity may hinder its spread and distribution, while its injection by cannula or needle may require moderate extrusion force and lead to uneven distribution or focal accumulation in tissues. Thus, new or modified delivery techniques and tools have emerged, particularly from East Asian physicians. One such technique is hyperdilution with diluents such as lidocaine or normal saline. CaHA hyperdilution appears to be more frequently used by experienced injectors who have varying methodologies. Here, we demonstrate the precise delivery of diluted filler to treat indications related to hereditary volume deficits, volume loss, or aging in the periorbital, nasolabial and submalar regions, marionette lines, and hollowed mid-facial areas. Regardless of age or indication, dilution eases filler delivery for the injector, while using lidocaine as the diluent decreases patient discomfort and minimizes pain. Increasing injection diluent volumes reduces filler thickness (viscosity) and facilitates its even spread, encouraging skin stimulation through more direct contact with tissues and minimizing unevenness. Our results effectively demonstrate that hyperdilution is an innovative and positive evolution in CaHA filler delivery.

Quantitative Top-Down Mass Spectrometry Identifies Proteoforms Differentially Released during Mechanical Stimulation of Mouse Skin.

Mechanotransduction refers to the processes whereby mechanical stimuli are converted into electrochemical signals that allow for the sensation of our surrounding environment through touch. Despite its fundamental role in our daily lives, the molecular and cellular mechanisms of mechanotransduction are not yet well-defined. Previous data suggest that keratinocytes may release factors that activate or modulate cutaneous sensory neuron terminals, including small molecules, lipids, peptides, proteins, and oligosaccharides. This study presents a first step toward identifying soluble mediators of keratinocyte-sensory neuron communication by evaluating the potential for top-down mass spectrometry to identify proteoforms released during 1 min of mechanical stimulation of mouse skin from naı̈ve animals. Overall, this study identified 47 proteoforms in the secretome of mouse hind paw skin, of which 14 were differentially released during mechanical stimulation, and includes proteins with known and previously unknown relevance to mechanotransduction. Finally, this study outlines a bioinformatic workflow that merges output from two complementary analysis platforms for top-down data and demonstrates the utility of this workflow for integrating quantitative and qualitative data.

Robotic Homunculus: Learning of Artificial Skin Representation in a Humanoid Robot Motivated by Primary Somatosensory Cortex

Using the iCub humanoid robot with an artificial pressure-sensitive skin, we investigate how representations of the whole skin surface resembling those found in primate primary somatosensory cortex can be formed from local tactile stimulations traversing the body of the physical robot. We employ the well-known self-organizing map algorithm and introduce its modification that makes it possible to restrict the maximum receptive field (MRF) size of neuron groups at the output layer. This is motivated by findings from biology where basic somatotopy of the cortical sheet seems to be prescribed genetically and connections are localized to particular regions. We explore different settings of the MRF and the effect of activity-independent (input-output connections constraints implemented by MRF) and activity-dependent (learning from skin stimulations) mechanisms on the formation of the tactile map. The framework conveniently allows one to specify prior knowledge regarding the skin topology and thus to effectively seed a particular representation that training shapes further. Furthermore, we show that the MRF modification facilitates learning in situations when concurrent stimulation at nonadjacent places occurs (“multitouch”). The procedure was sufficiently robust and not intensive on the data collection and can be applied to any robots where representation of their “skin” is desirable.

Assessment of pain quality reveals distinct differences between nociceptive innervation of low back fascia and muscle in humans.

Introduction/Objectives:Verbal descriptors are an important pain assessment parameter. The purpose of this study was to explore the ability to discriminate deep muscle pain and overlying fascia pain according to verbal descriptors and compare the pattern with skin stimulation (from previously published data).Methods:In 16 healthy human subjects, electrical stimulation was chosen to excite a broad spectrum of nociceptive primary afferents innervating the respective tissues. The 24-item Pain Perception Scale (Schmerzempfindungsskala [SES]) was used to determine the induced pain quality.Results:Overall, affective (P = 0.69) and sensory scores (P = 0.07) were not significantly different between muscle and fascia. Factor analysis of the sensory descriptors revealed a stable 3-factor solution distinguishing superficial thermal (“heat pain” identified by the items “burning,” “scalding,” and “hot”) from superficial mechanical (“sharp pain” identified by the items “cutting,” “tearing,” and “stinging”) and “deep pain” (identified by the items “beating,” “throbbing,” and “pounding”). The “deep pain” factor was more pronounced for muscle than fascia (P < 0.01), whereas the other 2 factors were more pronounced for fascia (both P < 0.01). The patterns of skin and fascia matched precisely in sensory factors and on single-item level.Conclusion:The differences in sensory descriptor patterns between muscle and fascia may potentially guide treatment towards muscle or fascia in low back pain physiotherapeutic regimes. The similarity of descriptor patterns between fascia and skin, both including the terms “burning” and “stinging,” opens the possibility that neuropathic back pain (when the dorsal ramus of the spinal nerve is affected) may be confused with low back pain of fascia origin.

A novel function of CCL27 in the localization of skin-homing CCR10+ lymphocytes

Abstract The skin contains an abundance of resident lymphocytes that play vital roles in the first line of defense. Dysregulation of the skin immune system could lead to diseases such as psoriasis and atopic dermatitis; studying the immune cells that contribute to skin immune homeostasis is crucial to understanding these diseases. Our lab has found that various subsets of skin-homing lymphocytes that express the chemokine receptor CCR10 have homeostatic functions. The skin specific ligand to CCR10 is CCL27. We found that the expression pattern of CCL27 in the skin of mice is similar to humans: low expression at a young age with a gradual upregulation into adulthood. This upregulation of CCL27 does not require the stimulation of skin colonizing bacteria, as germ free mice did not significantly differ from specific pathogen free mice in their expression of CCL27, suggesting an intrinsic regulatory mechanism for CCL27 expression. CCR10-expressing cells were found to concentrate near the hair follicles, suggesting a role for CCL27/CCR10 in the localization of these cells to specific microstructures. Preliminary analysis of skin-draining lymph node sections from CCR10+/EGFP vs CCR10EGFP/EGFP mice show differential localization of lymphocytes around the vessel-rich medulla. Further, lymphatic endothelial cells from the skin draining lymph nodes express CCL27. These findings indicate a novel role of CCL27 in directing the migration and localization of CCR10+ cells within the skin-draining lymph nodes and skin.

F193. What remains as transcranial cortical response after accounting for the contribution of somatosensory and auditory evoked responses?

Focal transcranial magnetic stimulation (TMS) induces somatosensory input due to excitation of peripheral trigeminal nerve branches as well as auditory input caused by the loud click produced during stimulus discharge. In a recent study, we have demonstrated that these peripheral sources of cortical activation make a strong contribution to the transcranial evoked potentials (TEPs) that can be recorded with EEG at the scalp. Here we investigated the components of the TEP after removal of multisensory contributions. In 10 healthy young volunteers, we applied single-pulse neuronavigated TMS using two coil orientations (perpendicular and parallel to the target gyrus) and two positions (superior frontal gyrus and superior parietal lobule) and recorded the TEPs. We also recorded the evoked EEG response in a sham condition during which the TMS click was given simultaneously with bipolar electrical skin stimulation at the site corresponding to the centre of the coil during real TMS. We applied a fitting procedure to the sham and real-TMS conditions to exclude the signal related to somatosensory and auditory processing from the transcranially evoked TMS response. Some of the standard peaks commonly reported in the TMS/EEG literature were reduced or modified, suggesting that they were also caused by multisensory peripheral stimulation. For example, this was the case for the negative deflection that appears at around 100 ms after single-pulse TMS. We also identified TEP components which were not changed after accounting for somatosensory and auditory EEG response. This uncovered TEP signal was sensitive to the direction of the coil orientation, showing statistical difference in time intervals that were not present in the original TEP. This study confirms the need to exclude the somatosensory and auditory confounds in order to have a deeper insight into the TMS/EEG results. The appropriate approach is to include a sham procedure that controls for the contribution of peripheral sensory stimulation to the TEPs. Our novel procedure renders it possible to study the brain response to direct magnetic stimulation of the cortex also in time intervals affected or covered by unwanted sensory inputs.

1030 Role of mast cells in psoriasis associated-pruritus

Whilst a key role of mast cells in itch (pruritogenic pruritus) is well-established, the exact underlying mechanisms remain to be fully elucidated. Here, we have examined the role of mast cells in psoriasis-associated pruritus. By immunofluorescence microscopy we confirmed not only that lesional psoriasis skin showed increased mast cell numbers, degranulation activity and overall innervation, but also an increased density of PAR2-positive nerve fibres. Moreover, the proximity of visualized nerve fibres and mast cells was increased suggesting enhanced mast cell-nerve interaction. To characterized mast cell related-itch pathways, healthy human skin was exposed in vitro for 18 hours to known pruritogens which induce mast cell activation such as compound 48/80, substance P (SP), and the selective proteinase-activated receptor 2 (PAR2)-activating peptide, SLIGKV, to mimic conditions of itch and neurogenic skin inflammation and to compare the expression of itch-associated genes with unexposed skin. RNA-Seq with DESeq2 was used for analysis of transcript expression. In organ-cultured healthy human skin, TSLP transcripts were upregulated 1.65, 1.53, and 1.59 fold following stimulation with 100 μg/ml of compound 48/80, 2 μM of SP and 100 μM of SLIGKV, respectively. In addition, SP stimulation upregulated IL31RA and TLR7 gene expression 3.22 and 2.56 fold, respectively, whilst stimulation with SLIGKV also upregulated MRGPRX2, TRPA1, and IL2RA 1.56, 2.21, and 1.76 fold, respectively. The differences in itch-associated genes, other than TSLP, upregulated following stimulation of skin with compound 48/80, SP, and SLIGKV may suggest that SP and PAR-2 agonists could induce itch through multiple, distinct and synergistic signalling pathways. Furthermore, these findings indicate that SP stimulation increases the sensitivity of the skin to potent pruritogens, such as IL-31 or TLR7 ligands, by upregulating their receptors.

Tactile-STAR: A Novel Tactile STimulator And Recorder System for Evaluating and Improving Tactile Perception.

Many neurological diseases impair the motor and somatosensory systems. While several different technologies are used in clinical practice to assess and improve motor functions, somatosensation is evaluated subjectively with qualitative clinical scales. Treatment of somatosensory deficits has received limited attention. To bridge the gap between the assessment and training of motor vs. somatosensory abilities, we designed, developed, and tested a novel, low-cost, two-component (bimanual) mechatronic system targeting tactile somatosensation: the Tactile-STAR—a tactile stimulator and recorder. The stimulator is an actuated pantograph structure driven by two servomotors, with an end-effector covered by a rubber material that can apply two different types of skin stimulation: brush and stretch. The stimulator has a modular design, and can be used to test the tactile perception in different parts of the body such as the hand, arm, leg, big toe, etc. The recorder is a passive pantograph that can measure hand motion using two potentiometers. The recorder can serve multiple purposes: participants can move its handle to match the direction and amplitude of the tactile stimulator, or they can use it as a master manipulator to control the tactile stimulator as a slave. Our ultimate goal is to assess and affect tactile acuity and somatosensory deficits. To demonstrate the feasibility of our novel system, we tested the Tactile-STAR with 16 healthy individuals and with three stroke survivors using the skin-brush stimulation. We verified that the system enables the mapping of tactile perception on the hand in both populations. We also tested the extent to which 30 min of training in healthy individuals led to an improvement of tactile perception. The results provide a first demonstration of the ability of this new system to characterize tactile perception in healthy individuals, as well as a quantification of the magnitude and pattern of tactile impairment in a small cohort of stroke survivors. The finding that short-term training with Tactile-STAR can improve the acuity of tactile perception in healthy individuals suggests that Tactile-STAR may have utility as a therapeutic intervention for somatosensory deficits.

Evidence Supporting a Role for Autonomic Modulation of C‐Low Threshold Mechanoreceptors

C‐low threshold mechanoreceptors (LTMRs) are a functionally distinct class of cutaneous sensory fibers believed to facilitate the sensing and coding of pleasurable touch. These afferents have also been implicated in neuropathic pain states including allodynia, in which normally innocuous tactile stimuli elicit painful sensations. The mechanisms that mediate changes in C‐LTMR function are incompletely understood. Autonomic activity has been implicated in the maintenance of various pain syndromes, yet increases in autonomic neural activity do not seem to influence the firing properties of cutaneous nociceptors. Autonomic modulation of cutaneous C‐LTMRs may contribute to allodynia and neuropathic pain, but this has not been studied. We developed an in vitro isolated truncal skin‐nerve preparation to study the recruitment properties of C‐LTMRs following optical stimulation of skin (TH::CHR2 mice) and the actions of modulatory transmitters when bath applied to the subcutaneous interior side of the skin. Extracellular spike recordings were obtained from dorsal cutaneous nerves. Optogenetic recruitment of C‐LTMRs was temperature sensitive with lower temperatures recruiting more units. Recruited C‐LTMRs had typical conduction velocities (ranging from 0.35 to 0.5 m/s) and an average spike half‐width of 0.53 ms (+/− 0.2ms). We assessed fatigability in response to repetitive optical stimuli at 10 Hz. Consistent with previous reports C‐LTMRs were highly fatigable, especially at higher temperatures. Application of acetylcholine resulted in increased spontaneous afferent activity, reduced C‐LTMR recruitment, and increased fatigability. Application of the cholinesterase inhibitor neostigmine also depressed C‐LTMR recruitment. Norepinephrine also decreased recruitment and increased fatigability but reduced the incidence of spontaneous activity. The norepinephrine transport inhibitor clomipramine also reduced C‐LTMR recruitment. Serotonin did not result in changes to recruitment or fatigability of C‐LTMRs, but increased spontaneous activity. However, the serotonin transport inhibitor citalopram did reduce C‐LTMR recruitment. Similarly, dopamine administration had no effect, but application of the dopamine transport inhibitor buproprion depressed C‐LTMR recruitment. We conclude that C‐LTMR activity can be modified by neuromodulatory transmission and studies are underway to further characterize this effect.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Muscarinic modulation of the Xenopus laevis tadpole spinal mechanosensory pathway

Muscarinic acetylcholine receptors (mAChRs) mediate effects of acetylcholine (ACh) in many systems, including those involved in spinal functions like locomotion. In Xenopus laevis tadpoles at two days old, a model vertebrate for motor control research, we investigated the role of mAChRs in the skin mechanosensory pathway. We found that mAChR activation by carbachol did not affect the sensory Rohon-Beard neuron properties. However, carbachol could hyperpolarise sensory interneurons and decrease their voltage responses to outward currents. Carbachol could increase the threshold for the mechanosensory pathway to start swimming, preventing the initiation of swimming at higher concentrations altogether. Recording from the sensory interneurons in carbachol showed that their spiking after skin stimulation was depressed. However, the general muscarinic antagonist atropine did not have a clear effect on the swimming threshold or the modulation of sensory interneuron membrane conductance. Our results suggest the skin mechanosensory pathway may be subject to muscarinic modulation in this simple vertebrate system.

Evaluation of "Energy Resonance by Cutaneous Stimulation" Among Women Treated by In Vitro Fertilization.

Pregnancy rate in in vitro fertilization (IVF) depends on many factors, such as the characteristics of the couple and the clinicobiological parameters. Interest in alternative and complementary medicine (ACM) for IVF is discussed because of the lack of scientific evidence. Energy resonance by cutaneous stimulation (ERCS), an acupuncture-like technique, consists of skin stimulation to transmit vibratory messages. The aim of this study was to evaluate the effect of ERCS on live birth rates (LBRs) in IVF. A prospective observation study was performed in the Unit of Assisted Reproductive Technologies of a University Teaching Hospital. Every woman who agreed to participate in this study and received a fresh embryo transfer (ET) after IVF or Intracytoplasmic Sperm Injection (ICSI) was included. Patients randomly underwent an ERCS session on the day of ET according to the schedule of the midwife performing this technique. The control group consisted of women undergoing ET under usual conditions. The main outcome measure was the LBR per transfer. Three-hundred-eighteen women were included, 120 in the ERCS + ET group and 198 in the ET without ERCS group. None of the women dropped out. The clinical characteristics in both groups were comparable. There was a significant difference in the clinical pregnancy rates, 31.7% in the ERCS group versus 21.7% in the No ERCS group (p = 0.037). The LBR in the ERCS group was nearly significantly higher, 29.2% versus 20.7% in the No ERCS group (p = 0,059). Women undergoing ERCS on the day of ET had a significantly higher IVF pregnancy rate. However, this methodology made not possible to draw conclusions about the mechanisms that induced the increase of IVF LBRs: placebo effect, "cocooning," or ERCS self-effect? Further well-conducted studies are strongly needed to assess ERCS efficacy.

Higher Network Activity Induced by Tactile Compared to Electrical Stimulation of Leech Mechanoreceptors.

The tiny ensemble of neurons in the leech ganglion can discriminate the locations of touch stimuli on the skin as precisely as a human fingertip. The leech uses this ability to locally bend the body-wall away from the stimulus. It is assumed that a three-layered feedforward network of pressure mechanoreceptors, interneurons, and motor neurons controls this behavior. Most previous studies identified and characterized the local bend network based on electrical stimulation of a single pressure mechanoreceptor, which was sufficient to trigger the local bend response. Recent studies showed, however, that up to six mechanoreceptors of three types innervating the stimulated patch of skin carry information about both touch intensity and location simultaneously. Therefore, we hypothesized that interneurons involved in the local bend network might require the temporally concerted inputs from the population of mechanoreceptors representing tactile stimuli, to decode the tactile information and to provide appropriate synaptic inputs to the motor neurons. We examined the influence of current injection into a single mechanoreceptor on activity of postsynaptic interneurons in the network and compared it to responses of interneurons to skin stimulation with different pressure intensities. We used voltage-sensitive dye imaging to monitor the graded membrane potential changes of all visible cells on the ventral side of the ganglion. Our results showed that stimulation of a single mechanoreceptor activates several local bend interneurons, consistent with previous intracellular studies. Tactile skin stimulation, however, evoked a more pronounced, longer-lasting, stimulus intensity-dependent network dynamics involving more interneurons. We concluded that the underlying local bend network enables a non-linear processing of tactile information provided by population of mechanoreceptors. This task requires a more complex network structure than previously assumed, probably containing polysynaptic interneuron connections and feedback loops. This small, experimentally well-accessible neuronal system highlights the general importance of selecting adequate sensory stimulation to investigate the network dynamics in the context of natural behavior.