Early effects of cardiopulmonary bypass surgery on retinal nerve fiber layer and ganglion cell layer.

PURPOSE: To determine the effects of cardiopulmonary bypass surgery on retinal nerve fiber layer, ganglion cell layer, and macula by optic coherens tomography (OCT). METHOD: Sixty-six eyes of 33 patients aged between 44 and 74 who were indicated for cardiopulmonary bypass surgery in the cardiovascular surgery clinic were included in the study. Routine ophthalmologic examinations of all patients were performed before and 1 week after surgery. In addition, 3D(H) Macula+5 Line Cross 12 × 9 mm mod and Peripapilar 3D Disk 6 × 6 mm mod data were analyzed with OCT (Topcon, Triton Swept Source-OKT, Tokyo, Japan) device. Peripapillary total, superior, inferior retinal nerve fiber layer (RNFL), optic disc cavity volume, cup-to-disc ratio, macular ganglion cell layer (GCL), macular thickness were compared before and after surgery. RESULTS: After cardiopulmonary bypass surgery, thickening was detected in the total RNFL (p<0.001), superior RNFL (p = 0.01) and inferior RNFL (p<0.001) layers. There was no change in the values of GCL, macular thickness, optic disc cupping volume, cup-to-disc ratio after surgery (p>0.05). There was a positive correlation (r = 0.392 p<0.05) between the patients' blood oxygen (PO2) values during bypass surgery with their post-surgical GCL+ values, and a negative correlation between optic disc cup volumes (r=-0.349 p<0.05). CONCLUSION: RNFL thickening has been detected in patients undergoing cardiopulmonary bypass surgery. This thickening may occur secondary to ischemic edema that occurs during surgery. Considering the late complications of ischemic edema in the RNFL, oxygen levels should be kept at an optimum level during surgery and long-term ophthalmologic follow-ups should be performed.

Parapapillary choroidal microvasculature dropout in eyes with primary open-angle glaucoma.

The purpose of this study was to evaluate how various parameters are related to microvasculature dropout (MvD) area measured using optical coherence tomography angiography (OCTA). We measured the area of MvD in 55 patients with primary open-angle glaucoma (POAG). Using OCTA, MvD area and peripapillary choroidal atrophy (PPA) area were assessed in a 4.5 mm × 4.5 mm region. The following were examined: circumpapillary nerve fiber layer (cpRNFL) thickness, optic disc area, optic disc cupping area, optic disc rim area, Humphrey Field Analyzer (HFA) 24/10-2 mean deviation (MD), and pattern standard deviation (PSD). The relationship between MvD area and each parameter was evaluated using Spearman's rank correlation coefficient analysis. Mean MvD area and PPA area were 0.18 ± 0.17 mm2 and 1.13 ± 0.72 mm2, respectively. MvD area was significantly correlated with optic disc rim area (p = 0.0017), cpRNFL (p = 0.0027), HFA 24/10-2 MD, and PSD (p < 0.001). In eyes with POAG, MvD area indicates the severity of glaucoma, which might be associated with structural changes in the peripapillary vasculature around the optic disc.

Impact of 24-Hour Intraocular Pressure on Optic Nerve Fiber Layer Thickness in Patients with Early Diabetic Retinopathy.

Background: The optic nerve fiber layer, composed of ganglion cell axons within the ganglion cell layer, undergoes thickness changes due to diabetic retinopathy. However, the relationship between intraocular pressure (IOP) and optic fiber layer thickness remains unclear. Objective: To investigate the correlation between 24-hour intraocular pressure and optic nerve fiber layer thickness in patients with early diabetic retinopathy. Methods: This retrospective study collected 353 patients with early diabetic retinopathy from January 2019 to December 2021. They were categorized into the retinopathy group (n = 153) and the control group (n = 200). 24-hour IOP and optic fiber layer thickness were assessed, and the correlation between them was analyzed. Results: The observation group exhibited significantly higher 24-hour IOP compared to the control group (16.64 ± 2.58 vs. 15.63 ± 2.52 mmHg, P < .001). Notably, the thickness of upper, lower, nasal, temporal, and average optic nerve fiber layers in the observation group decreased significantly (P < .001). Pearson linear correlation revealed significant negative associations between 24-hour IOP and upper, nasal, temporal, and mean optic nerve fiber layer thickness (R2 = -0.277, -0.399, -0.344, and -0.489, P < .05). The upper, lower, nasal, temporal, and mean optic fiber thickness demonstrated diagnostic value for non-early diabetic retinopathy in type 2 diabetes patients (P < .05), with mean optic fiber thickness displaying the highest diagnostic potential (area under the curve: 0.843, 95% Confidence Interval: 0.803-0.884, P < .001). Conclusions: Thinning of the optic nerve fiber layer in early diabetic retinopathy patients holds predictive value for the condition and exhibits a negative correlation with 24-hour intraocular pressure.

Proglucagon signalling in the rat Dorsomedial Hypothalamus - Physiology and high-fat diet-mediated alterations.

A relatively new pharmacological target in obesity treatment has been the preproglucagon (PPG) signalling, predominantly with glucagon-like peptide (GLP) 1 receptor agonists. As far as the PPG role within the digestive system is well recognised, its actions in the brain remain understudied. Here, we investigated PPG signalling in the Dorsomedial Hypothalamus (DMH), a structure involved in feeding regulation and metabolism, using in situ hybridisation, electrophysiology, and immunohistochemistry. Our experiments were performed on animals fed both control, and high-fat diet (HFD), uncovering HFD-mediated alterations. First, sensitivity to exendin-4 (Exn4, a GLP1R agonist) was shown to increase under HFD, with a higher number of responsive neurons. The amplitude of the response to both Exn4 and oxyntomodulin (Oxm) was also altered, diminishing its relationship with the cells' spontaneous firing rate. Not only neuronal sensitivity, but also GLP1 presence, and therefore possibly release, was influenced by HFD. Immunofluorescent labelling of the GLP1 showed changes in its density depending on the metabolic state (fasted/fed), but this effect was eliminated by HFD feeding. Interestingly, these dietary differences were absent after a period of restricted feeding, allowing for an anticipation of the alternating metabolic states, which suggests possible prevention of such outcome.

Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields.

PRCIS: The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping. PURPOSE: We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field. METHODS: This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations. RESULTS: The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 µm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 µm, respectively; differences between baseline and each follow-up visit were not statistically significant. CONCLUSIONS: The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.

Consumption of Coffee and Tea Is Associated with Macular Retinal Nerve Fiber Layer Thickness: Results from the UK Biobank.

Coffee and tea drinking are thought to be protective for the development and progression of neurodegenerative disorders. This study aims to investigate associations between coffee and tea consumption with macular retinal nerve fiber layer (mRNFL) thickness, a marker of neurodegeneration. After quality control and eligibility screening, 35,557 out of 67,321 United Kingdom (UK) Biobank participants from six assessment centers were included in this cross-sectional study. In the touchscreen questionnaire, participants were asked how many cups of coffee and tea were consumed daily on average over the last year. Self-reported coffee and tea consumption were divided into four categories including 0 cup/day, 0.5-1 cups/day, 2-3 cups/day, and ≥4 cups/day, respectively. The mRNFL thickness was measured by the optical coherence tomography (Topcon 3D OCT-1000 Mark II) and automatically analyzed by segmentation algorithms. After adjusting for covariates, coffee consumption was significantly associated with an increased mRNFL thickness (ß = 0.13, 95% CI = 0.01~0.25), which was more prominent in those who drank 2~3 cups coffee per day (ß = 0.16, 95% CI = 0.03~0.30). The mRNFL thickness was also significantly increased in tea drinkers (ß = 0.13, 95% CI = 0.01~0.26), especially for those who drank more than 4 cups of tea per day (ß = 0.15, 95% CI = 0.01~0.29). The positive associations with mRNFL thickness, indicating that both coffee and tea consumptions had likely neuroprotective potentials. Causal links and underlying mechanisms for these associations should be explored further.

Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

[Results of the application of complex physiotherapeutic neurostimulation in optical neuropathies of various genesis]. / Rezul'taty primeneniya kompleksnoi fizioterapevticheskoi neirostimulyatsii pri opticheskikh neiropatiyakh sosudistogo geneza.

Optical neuropathies (ON) are the outcome of many diseases of various origins. The main ones are classified as inflammatory, vascular and traumatic ON. ON lead to subatrophy of the optic nerve, but even after the completion of treatment, it is possible to improve visual functions by using physiotherapeutic means of ophthalmic rehabilitation. OBJECTIVE: To evaluate the effectiveness of complex physiotherapeutic neuro-ophthalmostimulation in case of ON of vascular origin. MATERIAL AND METHODS: The study included 60 patients (120 eyes) with a verified diagnosis of optic neuropathy of vascular origin, who were divided into 2 groups comparable in age, gender and anatomical and functional characteristics: the main group of 30 patients (60 eyes) and the control group - 30 patients (60 eyes), including 24 men and 36 women, mean age was 66.2±4.1 years, disease duration was 4.1±1.7 years. All patients underwent courses of conservative treatment with vitamins according to the available ophthalmological standards, repeating them 1-2 times a year, the last of which was six months before the present study. Physiotherapy courses and patients did not pass. 20 healthy volunteers were taken to create basic indicators of the «norm¼ of the applied research methods. Patients of the main group used a set of procedures: transcranial magnetic electrical stimulation, endonasal electrophoresis with the drug neuroprotector Semax 0.1%, oxybaric chamber and acupuncture. Patients in the control group were prescribed basic therapy, including taking the vitamin complex BEROCCA for 3 months. Breakpoints: before treatment and at times: 1st week, 12 weeks and 24 weeks after the course of treatment, according to the standard recommendations for international multicenter studies. The following were assessed: visual field boundaries (dilation meridians; in deg.), light sensitivity (MS, MD; in dB), indicators of the state of the retinal ganglion layer (GCS thickness, volume loss): Avg CCG (in µm), FLV, GLV (in %). RESULTS: When evaluating the results in patients of the main group who received complex neurostimulation, the therapeutic efficacy in a week after the end of treatment was 94%, in 12 weeks - in 88% and in 24 weeks - 83%, while in patients of the control group for all studied indicators showed only a positive trend and therapeutic efficacy did not exceed 30-42%. CONCLUSION: Under the influence of the developed neurostimulating complex, the activity of nerve cells objectively increases, leading to a significant increase in the boundaries of the field of view and light sensitivity and a decrease in global losses of the retinal ganglion complex and optic nerve.

Electrochemical modulation enhances the selectivity of peripheral neurostimulation in vivo.

Electrical nerve stimulation serves an expanding list of clinical applications, but it faces persistent challenges in selectively activating bundled nerve fibers. In this study, we investigated electrochemical modulation with an ion-selective membrane (ISM) and whether it, used together with electrical stimulation, may provide an approach for selective control of peripheral nerves. Guided by theoretical transport modeling and direct concentration measurements, we developed an implantable, multimodal ISM cuff capable of simultaneous electrical stimulation and focused Ca2+ depletion. Acutely implanting it on the sciatic nerve of a rat in vivo, we demonstrated that Ca2+ depletion could increase the sensitivity of the nerve to electrical stimulation. Furthermore, we found evidence that the effect of ion modulation would selectively influence functional components of the nerve, allowing selective activation by electrical current. Our results raise possibilities for improving functional selectivity of new and existing bioelectronic therapies, such as vagus nerve stimulation.

Differential effects of obstructive sleep apnea on the corneal subbasal nerve plexus and retinal nerve fiber layer.

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.

Optical coherence tomography findings in patients with transfusion-dependent ß-thalassemia.

BACKGROUND: Structural ophthalmologic findings have been reported in patients with ß-thalassemia due to chronic anemia, iron overload, and iron chelation therapy toxicity in few previous studies. We aimed to investigate structural ocular findings and their relationship with hematological parameters in patients with transfusion-dependent ß-thalassemia (TDT). METHODS: In this cross-sectional study, from January 2018 to January 2019, 39 patients with TDT over the age of 18 participated. Multicolor fundus imaging, optical coherence tomography (OCT), and blue light fundus autofluorescence imaging were performed for all patients and 27 age- and sex-matched controls. RESULTS: The mean age of patients was 28.6 ± 6.2 years. The central macular thickness and macular thicknesses in all quadrants were significantly thinner in patients than controls (P<0.05). None of the retinal nerve fiber layer (RNFL) measurements were significantly different between TDT patients and controls. There was a significantly negative correlation between hemoglobin with central macula thickness (r=-0.439, P=0.005). All measurements of macular subfield thickness were insignificantly thinner in patients with diabetes mellitus (DM) compared to the non-DM subgroup. CONCLUSIONS: Macular thickness was significantly thinner in central macula and entire quadrants in TDT patients compared to healthy individuals; however, all RNFL measurement thicknesses were comparable between the two groups. Close monitoring of TDT patients by periodic ophthalmologic examinations with more focus on diabetic patients, patients with severe anemia and iron overload should be warranted.

Short-term changes in Bruch's membrane opening-based morphometrics during the first week after trabeculectomy.

PURPOSE: To evaluate the dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head (ONH) using spectral-domain optical coherence tomography (SD-OCT) during the first week after glaucoma surgery by trabeculectomy with mitomycin C. METHODS: Prospective, longitudinal analysis of 25 eyes of 25 patients treated by trabeculectomy. Twenty-four eyes had evaluable postoperative SD-OCT examinations. Bruch's membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness were analyzed at baseline before surgery, 1 day, 2 to 3 days, and 1 week after surgery. Changes compared to baseline were correlated to intraocular pressure (IOP). RESULTS: One day after surgery, the mean BMO-MRW changed by + 26.17 µm, p = 0.001 (mean IOP reduction by 17.01 mmHg). This increase persisted on day 2-3 with a mean increase of BMO-MRW of + 25.33 µm, p = 0.001 (mean IOP reduction by 20.46 mmHg) and by week 1 with a mean BMO-MRW increase of + 33.17 µm, p < 0.001 (mean IOP reduction by 22.55 mmHg). The increase in BMO-MRW correlated significantly with the reduction of IOP on day 1 (Spearman's rho ρ = 0.656, p = 0.003) and d2-3 (Spearman's rho ρ = 0.479, p = 0.038). There was no statistically significant correlation found between the IOP and the increase in BMO-MRW in week 1. RNFL thickness showed no significant changes at day 1 as well as days 2-3 (p ≥ 0.078, respectively). It showed a small but significant increase in week 1 by 3.94 µm, p = 0.015. CONCLUSIONS: Structural reversal of disc cupping in BMO-MRW occurs as early as 1 day after trabeculectomy and correlates to the extent of the IOP reduction. During the whole first week after surgery, a strong increase in BMO-MRW can be noted. The changes in BMO-based parameters need to be considered when evaluating patients' longitudinal follow-up.

Spinal Neuronal GRK2 Contributes to Preventive Effect by Electroacupuncture on Cisplatin-Induced Peripheral Neuropathy in Mice.

BACKGROUND: The main symptoms of chemotherapy-induced peripheral neuropathy (CIPN) include pain and numbness. Neuronal G protein-coupled receptor kinase 2 (GRK2) plays an important role in various pain models. Cisplatin treatment can induce the activation of proinflammatory microglia in spinal cord. The purpose of this study was to investigate the role of spinal neuronal GRK2 in cisplatin-induced CIPN and in the prevention of CIPN by electroacupuncture (EA). METHODS: The pain and sensory deficit behaviors of mice were examined by von Frey test and adhesive removal test. The expression of neuronal GRK2 in the spinal cord is regulated by intraspinal injection of adeno-associated virus (AAV) containing neuron-specific promoters. The protein levels of GRK2, triggering receptor expressed on myeloid cells 2 (TREM2), and DNAX-activating protein of 12 kDa (DAP12) in spinal dorsal horn were detected by Western blot, the density of intraepidermal nerve fibers (IENFs) was detected by immunofluorescence, and microglia activation were evaluated by real-time polymerase chain reaction (PCR). RESULTS: In this study, cisplatin treatment led to the decrease of GRK2 expression in the dorsal horn of spinal cord. Overexpression of neuronal GRK2 in spinal cord by intraspinal injection of an AAV vector expressing GRK2 with human synapsin (hSyn) promotor significantly inhibited the loss of IENFs and alleviated the mechanical pain and sensory deficits induced by cisplatin. Real-time PCR analysis showed that the overexpression of neuronal GRK2 significantly inhibited the messenger RNA (mRNA) upregulation of proinflammatory cytokine interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), and M1 microglia marker cluster of differentiation (CD)16 induced by cisplatin. Furthermore, the TREM2 and DAP12, which has been demonstrated to play a role in microglia activation and in the development of CIPN, were also downregulated by overexpression of neuronal GRK2 in this study. Interestingly, preventive treatment with EA completely mimics the effect of overexpression of neuronal GRK2 in the spinal cord in this mouse model of cisplatin-induced CIPN. EA increased GRK2 level in spinal dorsal horn after cisplatin treatment. Intraspinal injection of AAV vector specifically downregulated neuronal GRK2, completely reversed the regulatory effect of EA on CIPN and microglia activation. All these indicated that the neuronal GRK2 mediated microglial activation contributed to the process of CIPN. CONCLUSIONS: Neuronal GRK2 in the spinal cord contributed to the preventive effect of EA on CIPN. The neuronal GRK2 may be a potential target for CIPN intervention.

Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers.

ATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.

[Effect of moxibustion on colonic mucosal injury and expression of CGRP positive nerve fibers of distal colonic mucosa in ulcerative colitis mice].

OBJECTIVE: To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points. METHODS: A total of 51 C57BL/6N mice were randomized into a 7-day control group (n=8), a 7-day model group (n=7), a 7-day moxibustion group (n=7), a 14-day control group (n=6), a 14-day model group (n=14) and a 14-day moxibustion group (n=9). In the model groups and the moxibustion groups, 2% dextran sulfate sodium (DSS) was given for 7-day free drinking to establish the UC model. Three days into modeling, moxibustion was applied at "Zusanli" (ST 36) in the 7-day moxibustion group and the 14-day moxibustion group, once a day, 10 min a time for 5 days and 12 days respectively. HE staining was used to observe the morphology of colonic tissue, the percentages of distal, middle and proximal colonic mucosal injury were calculated. Immunofluorescence staining was used to detected the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa. RESULTS: Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened (P<0.001), percentages of overall, distal, middle colonic mucosal injury were increased (P<0.001), the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were increased (P<0.001, P<0.05, P<0.01) in the 7-day model group. Compared with the 7-day model group, the expressions of positive nerve fibers of middle and distal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were decreased in the 7-day moxibustion group (P<0.05). Compared with the 14-day control group, the colon length was shortened (P<0.01), percentage of overall colonic mucosal injury was increased (P<0.001) in the 14-day model group. Compared with the 14-day model group, colon length was lengthened (P<0.05), percentage of overall colonic mucosal injury was decreased (P<0.05) in the 14-day moxibustion group. CONCLUSION: Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.

A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation.

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives-methylparaben and phenoxyethanol-but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.

Serotonin (5-hydroxytryptamine)-immunoreactive neurons in the brain of the viviparous fish Gambusia affinis.

The monoaminergic neurotransmitter serotonin (5-HT) acts as a neuromodulator and is associated with a wide range of functions in fish. In this investigation, 5-HT immunoreactivity was studied in the central nervous system (CNS) of the viviparous mosquitofish Gambusia affinis. 5-HT-immunoreactive (5-HT-ir) cells/fibres were observed throughout the subdivisions of ventral and dorsal telencephalon including the olfactory bulb. Several intensely stained 5-HT-ir cells and/or fibres were detected in different areas of the hypothalamus as well as the proximal pars distalis of the pituitary gland. 5-HT-ir cells were restricted to the dorsal and ventral part of the pretectal diencephalic cluster, but only fibres were detected in the anterior, ventromedial and posterior subdivisions of the thalamic nucleus and in the preglomerular complex. In the mesencephalon, 5-HT-ir perikarya, and fibres were seen in the optic tectum, midbrain tegmentum and torus semicircularis. A cluster of prominently labelled 5-HT-ir neurons was observed in the superior raphe nucleus, whereas numerous 5-HT-ir fibres were distributed throughout the rhombencephalic divisions. In addition, a bundle of rostrocaudally running 5-HT-ir fibres was noticed in the spinal cord. This is the first detailed neuroanatomical study in a viviparous teleost, reporting a widespread distribution of 5-HT-ir somata and fibres in the CNS. The results of this study provide new insights into the evolutionarily well conserved nature of the monoaminergic system in the CNS of vertebrates and suggest a role for 5-HT in regulation of several physiological, behavioural and neuroendocrine functions in viviparous teleosts.

Peculiarities of Neurostimulation by Intense Nanosecond Pulsed Electric Fields: How to Avoid Firing in Peripheral Nerve Fibers.

Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength-duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.

Change of ocular parameters in children with large cup-to-disc ratio and interocular cup-to-disc ratio asymmetry.

BACKGROUND: Enlarged optic disc cupping and interocular cup-to-disc ratio (CDR) asymmetry are often important indicators of glaucoma. Clinically, we occasionally encounter children with large CDR and interocular CDR asymmetry during vision screening. This study aimed to report longitudinal change of ocular parameters in children with large cup-to-disc ratio (CDR) and interocular CDR asymmetry. METHODS: This was a retrospective, observational case series of 160 eyes of 160 children with large CDR who visited a tertiary eye center from January 2010 to June 2016. Average CDR ≥ 0.6 were considered large CDR values, and CDR asymmetry was defined as an interocular difference ratio value greater than 0.2. All included patients showed interocular pressure (IOP) < 21 mmHg at least three ophthalmic examinations conducted at total intervals of at least 30 months. RESULTS: The mean age of children included in the study was 7.14 ± 2.42 years, with a follow-up period of 54.46 ± 19.82 months. Changes in refractive error and axial length were significantly different between initial and final examination (p < 0.001). However, optic nerve head (ONH) analysis and retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thicknesses were not significantly different between initial and final examination. In interocular comparisons of patients with CDR asymmetry, changes of refractive error, axial length, ONH analysis, and RNFL and mGCIPL thickness were not significantly different between the two eyes. CONCLUSIONS: There were no significant differences in the changes of ONH analysis, and RNFL and mGCIPL thicknesses in children with large CDR, or those with interocular CDR asymmetry over the study period. Our results provide helpful information for the establishment of guidelines for managing children with large CDR and interocular CDR asymmetry.

[Electroacupuncture and transcutaneous electrical acupoint stimulation relieve muscular inflammatory pain by activating afferent nerve fibers in different layers of "Liangqiu"(ST34) in rats].

OBJECTIVE: To compare the effect of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) of skin and muscle layers of "Liangqiu" (ST34) area on inflammatory muscular pain in rats, so as to study the role of different-layer afferent nerve fibers in acupuncture analgesia. METHODS: A total of 120 male SD rats were used in the present study, including 8 rats used for determining the excitatory threshold of Aδ(Ta) and C (Tc) afferent nerve fibers, 48 employed for comparing the analgesic effect of EA and TEAS at intensities of Ta and Tc, and 64 for observing the effect of EA and TAES stimulation of ipsilateral (Ipsi), contralateral (Contra) ST34 and ipsilateral LI4 at Ta and Tc intensities. Inflammatory muscle pain was induced by injection of complete Freund's adjuvant (CFA) into the right biceps femoris muscle. In the second part of the present study, 48 rats were randomly and equally divided into control, model, TEAS-Ta, TEAS-Tc, EA-Ta and EA-Tc groups, while in the 3rd part, 64 rats were randomly and equally divided into control, model, Ipsi-ST34-TEAS, Contra-ST34-TEAS, Ipsi-ST34-EA, Contra-ST34-EA, Ipsi-LI4-TEAS and Ipsi-LI4-EA groups. TEAS or EA was applied to the skin and muscle layers, respectively. Before and after modeling, the animal was forced to stand on a bipedal equilibrator, the difference in body mass distribution of both feet (bearing difference) was used to assess the pain severity. The frequency of myoelectrical discharges of the right bicep femoris muscle in responding to electrical stimulation of the spot between the 4th and 5th toes of the ipsilateral hindlimb at an intensity of two-folds of C-fiber excitatory threshold was recorded. RESULTS: 1) The bearing difference between the bilateral hindlimbs was markedly higher in the model group than in the control group (P<0.01), and significantly lower at the 2nd and 3rd day in the EA-Ta and EA-Tc, and TEAS-Tc groups relevant to the model group (P<0.05, P<0.01). 2) The frequency of C-fiber reflex induced electromyogram (EMG) activities were significantly decreased at 0 and 1 min after TEAS of both ipsilateral ST34 at Tc, and 0 min after TEAS of the contralateral ST34 at Tc (rather than at Ta and not LI4 even at Tc) in comparison with pre-TEAS, and 0, 1 and 2 min after TEAS of ipsilateral ST34 at Tc, and 0 min after TEAS of contra-ST34 at Tc compared with the model group, respectively (P<0.01, P<0.05). In comparison with pre-EA, the frequency of C-fiber reflex induced EMG activities were significantly decreased at 0 and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 and 2 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc (P<0.01, P<0.05).In comparison with the model group, the frequency of C-fiber reflex induced EMG activities are significantly decreased at 0, and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 ,2,and 3 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc, respectively (P<0.01, P<0.05). CONCLUSION: TEAS-ST34 at Tc and EA-ST34 at both Ta and Tc can alleviate pain behavior in inflammatory pain rats, which may be related to its effect in activating the afferent nerve fiber in different layers of ST34 area.