Human Nerve Research Articles

Dietary strategies may influence human nerves and emotions by regulating intestinal microbiota: an interesting hypothesis

SummaryThe human body hosts enormous diversity of microbiota. Recently, the importance of microbial communities to host physiology has been recognised. Evidence is now emerging that the bidirectional communication between the central nervous system and gastrointestinal tract may affect human nerves, cognition and behaviour through the gut‐brain axis (GBA). Although the connection between enteropathy and neurological diseases has been found, it now seems intestinal microorganisms represent the direct mediator of psychopathology. The interactions between host neurological function and intestinal microbiota suggested dietary is a possible way to alleviate psychopathological and neurodegenerative diseases. This review discusses the possible effect of intestinal microbiota on the changes of nerves and emotions in human brain. Maintaining healthy diet strategies should be an important part of preventing neurological diseases and psychopathologies caused by systemic metabolic changes. We hope to provide a novel insight for the design of dietary therapies from the perspective of GBA.

Characterization and Functional Analysis of CD44v6.CAR T Cells Endowed with a New Low-Affinity Nerve Growth Factor Receptor-Based Spacer.

Effectiveness of adoptively transferred chimeric antigen receptor (CAR) T cells strongly depends on the quality of CAR-mediated interaction of the effector cells with the target antigen on tumor cells. A major role in this interaction is played by the affinity of the single-chain variable fragment (scFv) for the antigen, and by the CAR design. In particular, the spacer domain may impact on the CAR T cell function by affecting the length and flexibility of the resulting CAR. This study addresses the need to improve the manufacturing process and the antitumor activity of CD44v6-specific CAR T cells by defining the optimal structure of a spacer region derived from the extracellular domain of the human low-affinity nerve growth factor receptor (LNGFR). We tailored the LNGFR spacer to modulate CAR length to efficiently recognize distal or proximal epitopes and to allow selection of transduced CAR T cells by the use of clinical-grade validated manufacturing systems. The different LNGFR spacers investigated in this study are responsible for the generation of CAR T cells with a different memory phenotype, which is mainly related to the level of CAR expression and the extent of the associated tonic signaling. In particular, the CD44v6-NWN2.CAR T cells are enriched in central memory cells and show improved in vitro functions in terms of killing capability, and in vivo antitumor activity against hematological and solid tumors. Clinical Trial Registration numbers: clinicaltrial.gov NCT04097301; ClinicalTrials.gov, NCT00423124.

Simulation of potential action of stimulated external alternating current (AC) in nerve cells using Hindmarsh-Rose model

This paper describes the simulation of potential actions that occur in nerve cells when given frequency variation as a stimulus. The simulation aims to determine the response of nerve cells to various combinations of currents in this case frequency. The simulation results showed that oscillations occur when the given frequency is 0.045 Hz. While the neural cell response occurs when the frequency between 0.055 Hz-0.065 Hz. The method carried out by the author is to modify the model of Hindmarsh-Rose nerve cells and then simulate it using Matlab programming language. Based on the research that has been done it can be concluded that at a frequency of 0.055 Hz a potential signal of action is formed and oscillates. In the human body, nerve cells and muscle cells are cells that have the ability of excitability (stimulated) because it has membrane potential. Short fluctuations of such cells, serve as electrical signals.

Histologic validation of optical coherence tomography-based three-dimensional morphometric measurements of the human optic nerve head: Methodology and preliminary results

PurposeTo compare the three-dimensional (3D) morphology of the deep load-bearing structures of the human optic nerve head (ONH) as revealed in vivo by spectral domain optical coherence tomography (SDOCT) with ex vivo quantitative 3D histology. MethodsSDOCT imaging of the ONH was performed in six eyes from three brain-dead organ donors on life-support equipment awaiting organ procurement (in vivo conditions). Following organ procurement (ex vivo conditions), the eyes were enucleated and underwent a pars plana vitrectomy followed by pressurization to physiologic IOP and immersion fixation. Ex vivo ONH morphology was obtained from high-fidelity episcopic fluorescent 3D reconstruction. Morphologic parameters of the observed ONH canal geometry and peripapillary choroid, as well as the shape, visibility and depth of the lamina cribrosa were compared between ex vivo and in vivo measurements using custom software to align, scale, and manually delineate the different regions of the ONH. ResultsThere was significant correspondence between in vivo and ex vivo measurements of the depth and shape of the lamina cribrosa, along with the size and shape of Bruch's membrane opening (BMO) and anterior scleral canal opening (ASCO). Weaker correspondence was observed for choroidal thickness; as expected, a thinner choroid was seen ex vivo due to loss of blood volume upon enucleation (−79.9%, p < 0.001). In addition, the lamina was shallower (−32.3%, p = 0.0019) and BMO was smaller ex vivo (−3.38%, p = 0.026), suggesting post mortem shrinkage of the fixed tissue. On average, while highly variable, only 31% of the anterior laminar surface was visible in vivo with SDOCT (p < 0.001). ConclusionsMorphologic parameters by SDOCT imaging of the deep ONH showed promising correspondence to histology metrics. Small but significant shrinkage artifact, along with large effects of exsanguination of the choroid, was seen in the ex vivo reconstructions of fixed tissues that may impact the quantification of ex vivo histoarchitecture, and this should be considered when developing models and biomarkers based on ex vivo imaging of fixed tissue. Lack of visibly of most of the lamina surface in SDOCT images is an important limitation to metrics and biomarkers based on in vivo images of the ONH deep tissues.

Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation

BackgroundNeuromodulation by electrical stimulation of the human cervical vagus nerve may be limited by adverse side effects due to stimulation of off-target organs. It may be possible to overcome this by spatially selective stimulation of peripheral nerves. Preliminary studies have shown this is possible using a cylindrical multielectrode human-sized nerve cuff in vagus nerve selective neuromodulation. New methodThe model-based optimisation method for multi-electrode geometric design is presented. The method was applied for vagus nerve cuff array and suggested two rings of 14 electrodes, 3 mm apart, with 0.4 mm electrode width and separation and length 0.5−3 mm, with stimulation through a pair in the same radial position on the two rings. The electrodes were fabricated using PDMS-embedded stainless steel foil and PEDOT: pTS coating. ResultsIn the cervical vagus nerve in anaesthetised sheep, it was possible to selectively reduce the respiratory breath rate (RBR) by 85 ± 5% without affecting heart rate, or selectively reduce heart rate (HR) by 20 ± 7% without affecting respiratory rate. The cardiac- and pulmonary-specific sites on the nerve cross-sectional perimeter were localised with a radial separation of 105 ± 5 degrees (P < 0.01, N = 24 in 12 sheep). ConclusionsResults suggest organotopic or function-specific organisation of neural fibres in the cervical vagus nerve. The optimised electrode array demonstrated selective electrical neuromodulation without adverse side effects. It may be possible to translate this to improved treatment by electrical autonomic neuromodulation for currently intractable conditions.

Whole-Genome Sequence Data Suggest Environmental Adaptation of Ethiopian Sheep Populations.

Great progress has been made over recent years in the identification of selection signatures in the genomes of livestock species. This work has primarily been carried out in commercial breeds for which the dominant selection pressures are associated with artificial selection. As agriculture and food security are likely to be strongly affected by climate change, a better understanding of environment-imposed selection on agricultural species is warranted. Ethiopia is an ideal setting to investigate environmental adaptation in livestock due to its wide variation in geo-climatic characteristics and the extensive genetic and phenotypic variation of its livestock. Here, we identified over three million single nucleotide variants across 12 Ethiopian sheep populations and applied landscape genomics approaches to investigate the association between these variants and environmental variables. Our results suggest that environmental adaptation for precipitation-related variables is stronger than that related to altitude or temperature, consistent with large-scale meta-analyses of selection pressure across species. The set of genes showing association with environmental variables was enriched for genes highly expressed in human blood and nerve tissues. There was also evidence of enrichment for genes associated with high-altitude adaptation although no strong association was identified with hypoxia-inducible-factor (HIF) genes. One of the strongest altitude-related signals was for a collagen gene, consistent with previous studies of high-altitude adaptation. Several altitude-associated genes also showed evidence of adaptation with temperature, suggesting a relationship between responses to these environmental factors. These results provide a foundation to investigate further the effects of climatic variables on small ruminant populations.

Rapid and efficient immunomagnetic isolation of endothelial cells from human peripheral nerves

Endothelial cells (ECs) have gained an increased scientific focus since they were reported to provide guidance for Schwann cells and subsequently following axons after nerve injuries. However, previous protocols for the isolation of nerve-derived ECs from human nerves are ineffective regarding time and yield. Therefore, we established a novel and efficient protocol for the isolation of ECs from human peripheral nerves by means of immunomagnetic CD31-antibody conjugated Dynabeads and assessed the purity of the isolated cells. The easy-to-follow and time-effective isolation method allows the isolation of > 95% pure ECs. The isolated ECs were shown to express highly specific EC marker proteins and revealed functional properties by formation of CD31 and VE-cadherin positive adherens junctions, as well as ZO-1 positive tight-junctions. Moreover, the formation of capillary EC-tubes was observed in-vitro. The novel protocol for the isolation of human nerve-derived ECs allows and simplifies the usage of ECs in research of the human blood-nerve-barrier and peripheral nerve regeneration. Additionally, a potential experimental application of patient-derived nerve ECs in the in-vitro vascularization of artificial nerve grafts is feasible.

Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol.

Injuries to the peripheral nerves represent a frequent cause of permanent disability in adults. The repair of large nerve lesions involves the use of autografts, but they have several inherent limitations. Overcoming these limitations, the use of decellularized nerve matrix has emerged as a promising treatment in tissue regenerative medicine. Here, we generate longer human decellularized nerve segments with a novel decellularization method, using nonionic, zwitterionic, and enzymatic incubations. Efficiency of decellularization was measured by DNA quantification and cell remnant analysis (myelin, S100, neurofilament). The evaluation of the extracellular matrix (collagen, laminin, and glycosaminoglycans) preservation was carried out by enzyme-linked immunosorbent assay (ELISA) or biochemical methods, along with histological and immunofluorescence analysis. Moreover, biomechanical properties and cytocompatibility were tested. Results showed that the decellularized nerves generated with this protocol have a concentration of DNA below the threshold of 50ng/mg of dry tissue. Furthermore, myelin, S100, and MHCII proteins were absent, although some neurofilament remnants could be observed. Moreover, extracellular matrix proteins were well maintained, as well as the biomechanical properties, and the decellularized nerve matrix did not generate cytotoxicity. These results show that our method is effective for the generation of decellularized human nerve grafts. The generation of longer decellularized nerve segments would allow the understanding of the regenerative neurobiology after nerve injuries in both clinical assays and bigger animal models. Effective decellularization of human nerve matrix for regenerative medicine with a novel protocol. Combination of zwitterionic, non-ionic detergents, hyperosmotic solution and nuclease enzyme treatment remove cell remnants, maintain collagen, laminin and biomechanics without generating cytotoxic leachables.

Parasympathetic neurons in the human submandibular ganglion

The submandibular ganglion (SMG) contains parasympathetic neurons which innervate the submandibular gland. In this study, immunohistochemistry for vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), choline acetyltransferase (ChAT), dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), and the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2) was performed on the human SMG. In the SMG, 17.5 % and 8.9 % of parasympathetic neurons were immunoreactive for VIP and TRPV2, respectively. SMG neurons mostly contained ChAT- and DBH-immunoreactivity. In addition, subpopulations of SMG neurons were surrounded by VIP (69.6 %)-, TRPV2 (54.4 %)- and DBH (9.5 %)-immunoreactive (-ir) nerve fibers. SMG neurons with pericellular VIP- and TRPV2-ir nerve fibers were significantly larger than VIP- and TRPV2-ir SMG neurons, respectively. Other neurochemical substances were rare in the SMG. In the human submandibular gland, TRPV1- and TRPV2-ir nerve fiber profiles were seen around blood vessels. Double fluorescence method also demonstrated that TRPV2-ir nerve fiber profiles were located around myoepithelial and acinar cells in the submandibular gland. VIP and TRPV2 are probably expressed by both pre- and post-ganglionic neurons innervating the submandibular and sublingual glands. VIP, DBH and TRPV2 may have functions about regulation of salivary components in the salivary glands and neuronal activity in the SMG.

Preparation of human decellularized peripheral nerve allograft using amphoteric detergent and nuclease.

Animal studies have shown that amphoteric detergent and nuclease (DNase I and ribonuclease A) is the most reliable decellularization method of the peripheral nerve. However, the optimal combination of chemical reagents for decellularization of human nerve allograft needs further investigation. To find the optimal protocol to remove the immunogenic cellular components of the nerve tissue and preserve the basal lamina and extracellular matrix and whether the optimal protocol can be applied to larger-diameter human peripheral nerves, in this study, we decellularized the median and sural nerves from the cadavers with two different methods: nonionic and anionic detergents (Triton X-100 and sodium deoxycholate) and amphoteric detergent and nuclease (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), deoxyribonuclease I, and ribonuclease A). All cellular components were successfully removed from the median and sural nerves by amphoteric detergent and nuclease. Not all cellular components were removed from the median nerve by nonionic and anionic detergent. Both median and sural nerves treated with amphoteric detergent and nuclease maintained a completely intact extracellular matrix. Treatment with nonionic and anionic detergent decreased collagen content in both median and sural nerves, while the amphoteric detergent and nuclease treatment did not reduce collagen content. In addition, a contact cytotoxicity assay revealed that the nerves decellularized by amphoteric detergent and nuclease was biocompatible. Strength failure testing demonstrated that the biomechanical properties of nerves decellularized with amphoteric detergent and nuclease were comparable to those of fresh controls. Decellularization with amphoteric detergent and nuclease better remove cellular components and better preserve extracellular matrix than decellularization with nonionic and anionic detergents, even in large-diameter human peripheral nerves. In Korea, cadaveric studies are not yet legally subject to Institutional Review Board review.

The role of antibodies to peripheral nerve antigens in pathogenesis and laboratory evaluation of immune-mediated neuropathies

Detection of antiganglioside autoantibodies and their association with clinically defined subtypes implicate an autoimmune mechanism of peripheraland cranial nerve damage in peripheral neuropathies. Increased titer of antibodies that react with human peripheral nerve antigens have been reported in patients with motor neuropathy including Guillain-Barré syndrome,chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and sensory motor neuropathy. This study represents review of the data related to increased titers of anti-glucoconjugate antibodies in different autoimmune neuropathies and their correlation with existence of structural homology between bacterial and glycoconjugated structures, as a basis for understanding the immune pathological response to glycoproteins and glycolipids present in the human peripheral nerve as target antigens in autoimmune neuropathies. Evaluation of presence and increased level of autoantibodies against peripheral nerve antigens could be an important parameter in laboratory evaluation, diagnosis and prognosis of autoimmune neuropathies and contribute in more efficient therapeutic approaches in treatment of these pathological conditions. Keywords: anti-glycoconjugate antibodies, anti-ganglioside antibodies, peripheral nerves, autoimmune neuropathies

Light‐Field imaging of the human optic nerve head at different wavelengths—a case study

PurposeOne strong risk factor for glaucoma is a suspicious optic nerve head appearance with an abnormal cupping or an increase in the cup‐to‐disc ratio. To measure such geometric characteristics, typically scanning systems like OCT or SLO are used. We present that one‐shot 3D retinal imaging and measuring with a commercial fundus camera using an industrial light‐field camera is possible and works best in the green spectrum.MethodsTo demonstrate 3D imaging at the human optic nerve head (ONH), we examined one eye with suspected glaucoma (patient:37 years, male). ONH centered 30° images of the right eye were taken after pupil dilatation with Tropicamid with a Zeiss FF450 fundus camera (Carl Zeiss Meditec AG, Germany), to which an industrial light‐field camera (Raytrix GmbH, Germany) was attached. The images were taken at 450 nm, 520 nm, 600 nm and 650 nm centroid wavelengths, 40 nm bandwidth each. The maximum depth of the papilla was determined in virtual depth (VD) using the Raytrix software (RxLive, Raytrix GmbH, Germany). The results were compared among each other concerning the vessel contrast, quantity of measurement points and subjectively where they were found.ResultsThe light‐field images showed clearly the ONH in 3D. The highest image contrast was found at 450 nm, whereby the contrast decreases with increasing illumination wavelengths. Most measurement points around the papilla were found at 520 nm followed by 450 nm with a slightly lower number. At 600 nm, the number of measurement points was significantly reduced. Worst results were found at 650 nm. Plausible measurement points were only found in image regions with high contrast. Those regions were vessel borders and the papilla border.ConclusionsUsing the light‐field technique in fundus photography, it is possible to image and to measure the ONH in 3D. Screening for glaucoma and glaucoma diagnosis can be much improved taking into account that, in principle, classical fundus imaging offer only 2D data.

A genetic mouse model with postnatal Nf1 and p53 loss recapitulates the histology and transcriptome of human malignant peripheral nerve sheath tumor.

BackgroundMalignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of NF1 and cooperating tumor suppressors, including CDKN2A/B, PRC2, and p53, is found in most MPNST. Inactivation of LATS1/2 of the Hippo pathway was recently shown to cause tumors resembling MPNST histologically, although Hippo pathway mutations are rarely found in MPNST. Because existing genetically engineered mouse (GEM) models of MPNST do not recapitulate some of the key genetic features of human MPNST, we aimed to establish a GEM-MPNST model that recapitulated the human disease genetically, histologically, and molecularly.MethodsWe combined 2 genetically modified alleles, an Nf1;Trp53 cis-conditional allele and an inducible Plp-CreER allele (NP-Plp), to model the somatic, possibly postnatal, mutational events in human MPNST. We also generated conditional Lats1;Lats2 knockout mice. We performed histopathologic analyses of mouse MPNST models and transcriptomic comparison of mouse models and human nerve sheath tumors.ResultsPostnatal Nf1;Trp53 cis-deletion resulted in GEM-MPNST that were histologically more similar to human MPNST than the widely used germline Nf1;Trp53 cis-heterozygous (NPcis) model and showed partial loss of H3K27me3. At the transcriptome level, Nf1;p53-driven GEM-MPNST were distinct from Lats-driven GEM-MPNST and resembled human MPNST more closely than do Lats-driven tumors.ConclusionsThe NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly.

Action potential subpopulations within human muscle sympathetic nerve activity: Discharge properties and governing mechanisms.

Sympathetic emissions directed towards the skeletal muscle circulation - muscle sympathetic nerve activity (MSNA) - represent a key mechanism for maintaining homeostasis and supporting human survival during physiological stress. Pulse-rhythmic bursts formed by the synchronous discharge of differently-sized sympathetic action potentials (APs) represent the primary characteristic of MSNA. Of the APs firing under baseline conditions (reflecting low-threshold c-fibre activity), a range of subpopulations exists, of which three general categories can be discussed based on their peak-to-peak amplitude in the filtered raw neurogram - small, medium, and large. These subpopulations express nonuniform discharge, recruitment, and synchronization patterns. The subpopulation of medium APs fires synchronously in most bursts, while the subpopulations of small and large APs fire less often. However, 30% of total AP discharge occurs asynchronously between sympathetic bursts, a pattern expressed most often by small APs. In response to physiological stress (e.g., baroreflex unloading), the subpopulation of medium APs exhibits the largest increase in firing probability and a subpopulation of previously-silent larger and faster-conducting APs (reflecting high-threshold c-fibre activity) becomes recruited. Heterogeneous discharge, synchronization, and recruitment thresholds among AP subpopulations stem from differential regulation within the sympathetic organization including the arterial baroreflex and paravertebral ganglia. Indeed, the arterial baroreflex strongly regulates medium APs at baseline and enhances its control over this subpopulation during periods of baroreflex unloading. Conversely, small and large APs express weak baroreflex control. Trimethaphan infusion has revealed that ganglionic processes including nicotinic and non-nicotinic mechanisms may contribute to heterogenous firing behaviours among low-threshold AP subpopulations. This review highlights recent work revealing new insight to the discharge properties expressed by, and mechanisms governing, AP subpopulations within human MSNA.

Register of the human brain acoustic area spectrum

Abstract. Last years, there were developed methods based on the human brain and body acoustic signals application. We consider human brain micro vibrations as an ancient, highly reliable, relatively rapid channel of the central nervous system with all the organism cells and structures. There is offered a method of the human brain acoustic area spectrum analysis and registration. Experimental sample “Register of the human brain micro vibrations spectrum is developed. The model of the human brain acoustic area generation is offered – neurovascular reflex and related with human brain blood vessels smooth muscularity nerve cells metabolism. In comparison with classical EEG, it is demonstrated that acoustic encephalogram also reflects human brain neuroreflex activity. Piezoelectric sensors, which feature in silicone membrane existence, are investigated. Such type of construction allowed to register human brain mechanical vibrations in the gamut from 0.1 up to 27 Hz. Spectral analysis is specific in that signal integration time is 160 seconds. Meanwhile, 12600 spectral harmonics of the human brain reticular activating system were reliably extracted. For convenience, all the acoustic area spectrum of the human brain was shrunk into segmental frame of reference which is frequency structured matrix of functional conditions multiplicity “multiple arousal” of 24х625 frequency cells size. All the developed technologies and device might be used for the organism adaptation estimations, psycho-emotional conditions estimations and functional-topical diagnosis of the internal parts of the human body.

Flap Neurotization in Breast Reconstruction with Nerve Allografts: 1-year Clinical Outcomes

Background:Autologous breast reconstruction is widely regarded as the gold standard approach following mastectomy. However, the lack of sensation continues to present a reconstructive challenge. In this study, clinical outcomes following abdominal flap neurotization with processed human nerve allograft were investigated.Methods:In this prospective analysis, patients who underwent microsurgical breast reconstruction with (Group 1) or without (Group 2) abdominal flap neurotization at a single institution were investigated. Processed human nerve allograft (Avance, AxoGen, Alachua, Fla.) was used in all cases of flap neurotization. Only patients with a follow-up of ≥12 months were included. Cutaneous pressure threshold was tested using Semmes-Weinstein monofilaments (SWMF) at 9 pre-defined locations.Results:A total of 59 patients (96 breasts) were enrolled into the registry. Of these, 22 patients (Group 1: N = 15, 22 breasts; Group 2: N = 7, 14 breasts) had a complete data set with ≥12 months follow-up. Measuring cutaneous pressure thresholds, we observed a greater likelihood for return of protective sensation (SWMF ≤ 4.31) in neurotized breasts in 8 of the 9 examined zones. Additionally, flap neurotization was associated with a greater likelihood for return of protective sensation in the majority of the reconstructed breast—that is, ≥5 zones (55% versus 7%; P < 0.01).Conclusion:Flap neurotization using processed nerve allograft resulted in a greater degree of return of protective sensation to the reconstructed breast than reconstructions without neurotization at ≥12 months.

Healthy Elder: Brain Stimulation Game for the Elderly to Reduce the Risk of Dementia

Abstract In general, everyone will experience a period of growth, starting from infants to children to adults. There will come a time when a person’s growth stops and decreases. When cognitive capabilities are not used often, it will decline, and this phenomenon is known as cognitive impairment. The most common form of cognitive impairment is dementia. Dementia is a degenerative disease that cannot be cured with the usual treatment techniques for physical degenerative diseases, such as surgery or physical contact. It is because this disease attacks the human nerve. One method that can be done is to prevent or reduce the risk of dementia by stimulating the brain. To implement this method, the researchers made a game that can stimulate the brain. The researcher used the Game Development Life Cycle (GDLC) method in the process of making the game. The test was conducted at Berea Nursing Home and Pusaka 41 Nursing Home. The result shows that out of 30 people who were tested, 19 people showed improvement in terms of their cognitive capabilities in seven days.

Neurons populating the rectal extrinsic nerves in humans express neuronal and Schwann cell markers

AbstractBackgroundIn mice, Schwann cell (SC) progenitors give rise to autonomic ganglion cells and migrate into the gut to become enteric neurons. It is unknown whether SC progenitors have a similar fate in humans. In search of evidence for human SC‐derived neurogenesis in the gastrointestinal (GI) tract, we studied the rectums from cadaveric controls and children with anorectal malformations (ARM).MethodsWe analyzed distal rectal tissue taken at autopsy from 10 children with normal GI tracts and resected rectal specimens in 48 cases of ARM. Of these specimens, 6 had neurons within the extrinsic rectal innervation. These were further investigated with immunohistochemistry for neuronal and SC/glial markers.Key ResultsPerirectal tissue from control and ARM contained GLUT1‐positive extrinsic nerves, many containing neurons. SC/glial markers (SOX10, CDH19, and PLP1) were expressed by glia in the enteric nervous system and perirectal nerves, while MPZ predominated only in glia of perirectal nerves, in both control and ARM. Neurons in perirectal nerves were 61% larger in ARM samples and co‐expressed SOX10 (81%), PLP1 (73%), and CDH19 (56%). In ARM, cytoplasmic SOX10 was co‐expressed with neuronal antigens in ~57% of submucosal and myenteric neurons, vs. ~3% in control. Furthermore, intrinsic gut neurons in ARM specimens co‐expressed PLP1 (18%) and CDH19 (18%); however, neuronal co‐expression of PLP1 and CDH19 was rarely (&lt;2%) observed in controls.Conclusions &amp; InferencesDual expression of glial and neuronal markers in rectal and perirectal neurons support a model of Schwann cell‐derived neurogenesis in the innervation of the human GI tract.

Medicinal cupping in the eyes of graph theory

Medicinal cupping is one of the traditional treatment methods that is trusted to give many benefits to the human health and still practising by various culture and societies around the world. The purposes of this treatment are to allow the toxin leaves the body,to stimulate the muscles and also helping in healing process for various diseases. The process start by placing special heated cups on specific points to create suction, then the points will be punctured. Each disease has specific cupping points to be cupped which located on the human nerves system. All the points actually connected to each other where a simple graph can be formed. Since there are limited studies that discuss medicinal cupping in a mathematics view, thus this research is conducted to introduce the easiest way on demonstrating the cupping points on the human nerves system by using the idea of graph. Hence, new definition of nerve vertex, nerve edge and nerve graph will be defined. Moreover, the idea of graph colouring will be applied to determine the optimal number of cupping points.

Slowly conducting potentials in human sensory nerves

BackgroundIn clinical practice, small myelinated sensory fibers, Aδ-fibers, conveying mainly pain and temperature sensations, cannot be examined with available nerve conduction study techniques. Currently, these fibers can only be examined with experimental or very specialized and not commonly available nerve conduction techniques, or only indirectly with cerebral evoked potentials. New MethodThis study uses equipment and methods available in clinical neurophysiology laboratories to record from human sensory nerves ≥1000 averaged responses to focal, non-painful stimuli applied by a special electrode to epidermal nerves. The averaged responses to odd numbered stimuli are compared to the averaged responses to even numbered stimuli. An algorithm identifies potentials common in both averages. The 99th and 99.9th percentiles for this algorithm are obtained from control records without stimulation and applied to records with stimulation to identify potentials resulting from stimulation of intraepidermal nerves. ResultsThe algorithm identifies numerous negative and positive potentials as being different from controls at the 99th and 99.9th percentile levels. The conduction velocities of the potentials range from of 1.3–29.9 m/s and are compatible with conduction velocities of Aδ-fibers. Comparison with existing Method(s)No existing methods. ConclusionsThe stimulation, recording and data analysis methods used in this study can be applied in the clinical EMG laboratory to identify Aδ-fibers in human sensory nerves.