Determining the Correct Resection Level in Patients with Hirschsprung Disease Using Contrast Enema and Full Thickness Biopsies: Can the Diagnostic Accuracy be Improved by Examining Submucosal Nerve Fiber Thickness?

BACKGROUND: Intraoperative resection level in patients with Hirschsprung disease (HD) is determined by contrast enema, surgeon's intraoperative judgement and full thickness biopsy (FTB) identifying ganglia. This study aims to evaluate diagnostic accuracy of contrast enema and FTB in determination of resection level and whether this can be improved by measuring submucosal nerve fiber diameter. METHODS: We retrospectively analyzed contrast enema and intraoperative FTBs obtained in our center, determining diagnostic accuracy for level of resection. Gold standard was pathological examination of resection specimen. Secondly, we matched transition zone pull-through (TZPT) patients with non-TZPT patients, based on age and length of resected bowel, to blindly compare nerve fibers diameters between two groups using group comparison. RESULTS: From 2000-2021, 209 patients underwent HD surgery of whom 180 patients (138 males; median age at surgery: 13 weeks) with 18 TZPTs (10%) were included. Positive predictive value of contrast enema was 65.1%. No caliber change was found in patients with total colon aganglionosis (TCA). Negative predictive value of surgeon's intraoperative judgement and FTB in determining resection level was 79.0% and 90.0% (91.2% single-stage, 84.4% two-stage surgery) respectively. Mean nerve fiber diameter in TZPT was 25.01 µm (SD= 5.63) and in non-TZPT 24.35 µm (SD= 6.75) (p = 0.813). CONCLUSION: Determination of resection level with combination of contrast enema, surgeon's intraoperative judgement and FTB results in sufficient diagnostic accuracy in patients with HD. If no caliber change is seen with contrast enema, TCA should be considered. Resection level or transition zone cannot be determined by assessment of submucosal nerve fiber diameter in FTB. TYPE OF STUDY: clinical research paper.

A Computational Model of a Single Auditory Nerve Fiber for Electric-Acoustic Stimulation.

Cochlear implant (CI) recipients with preserved acoustic low-frequency hearing in the implanted ear are a growing group among traditional CI users who benefit from hybrid electric-acoustic stimulation (EAS). However, combined ipsilateral electric and acoustic stimulation also introduces interactions between the two modalities that can affect the performance of EAS users. A computational model of a single auditory nerve fiber that is excited by EAS was developed to study the interaction between electric and acoustic stimulation. Two existing models of sole electric or acoustic stimulation were coupled to simulate responses to combined EAS. Different methods of combining both models were implemented. In the coupled model variant, the refractoriness of the simulated fiber leads to suppressive interaction between electrically evoked and acoustically evoked spikes as well as spontaneous activity. The second model variant is an uncoupled EAS model without electric-acoustic interaction. By comparing predictions between the coupled and the noninteracting EAS model, it was possible to infer electric-acoustic interaction at the level of the auditory nerve. The EAS model was used to simulate fiber populations with realistic inter-unit variability, where each unit was represented by the single-fiber model. Predicted thresholds and dynamic ranges, spike rates, latencies, jitter, and vector strengths were compared to empirical data. The presented EAS model provides a framework for future studies of peripheral electric-acoustic interaction.

Alcohol extract from Vernonia anthelmintica willd (L.) seed counteracts stress-induced murine hair follicle growth inhibition.

BACKGROUND: Vernonia anthelmintica (L.) willd is a traditional urgur herb in China for a long history. Its alcohol extract (AVE) has been proved to promote hair follicle growth in C57BL/6 mice. We conducted this study to investigate the hair-growth effects of AVE in stressed mice and its possible mechanism of action. METHODS: The hair-follicle growth effects of AVE were examined by in vivo and in vitro study. We exposed C57BL/6 male mice to chronic restraint stress to induce murine hair follicle growth inhibition. The effects of AVE were examined by histological analysis, immunofluorescence for Ki67 and cytokeratin 19 immunoreactivity, western blot assay in tyrosinase and related proteins expressions and immunofluorescence for nerve fibers. In organ culture of mouse vibrissae follicles, we used substance P as a catagen-inducing factor of hair follicle growth, and measured the elongation of hair shafts and expression of neurokinin-1 receptor protein by application of AVE. RESULTS: Our results showed that AVE counteract murine hair follicle growth inhibition caused by chronic restraint stress via inducing the conversion of telogen to anagen and inhibiting catagen premature, increasing bulb keratinocytes and bulge stem cells proliferation, promoting melanogenesis, and reducing the numbers of substance P and calcitonin gene-related peptide nerve fibers. Furthermore, AVE also counteracted murine hair follicle growth inhibition caused by substance P in organ culture. CONCLUSION: These results suggest that AVE counteract stress-induced hair follicle growth inhibition in C57BL/6 mice in vivo and in vitro, and may be an effective new candidate for treatment of stress-induced hair loss.

Tinnitus Treatment Using Noninvasive and Minimally Invasive Electric Stimulation: Experimental Design and Feasibility.

Noninvasive transcranial or minimally invasive transtympanic electric stimulation may offer a desirable treatment option for tinnitus because it can activate the deafferented auditory nerve fibers while posing little to no risk to hearing. Here, we built a flexible research interface to generate and control accurately charge-balanced current stimulation as well as a head-mounted instrument capable of holding a transtympanic electrode steady for hours. We then investigated the short-term effect of a limited set of electric stimulation parameters on tinnitus in 10 adults with chronic tinnitus. The preliminary results showed that 63% of conditions of electric stimulation produced some degree of tinnitus reduction, with total disappearance of tinnitus in six subjects in response to at least one condition. The present study also found significant side effects such as visual, tactile, and even pain sensations during electric stimulation. In addition to masking and residual inhibition, neuroplasticity is likely involved in the observed tinnitus reduction. To translate the present electric stimulation into a safe and effective tinnitus treatment option, we need to optimize stimulation parameters that activate the deafferented auditory nerve fibers and reliably suppress tinnitus, with minimal side effects and tolerable sensations. Noninvasive or minimally invasive electric stimulation can be integrated with sound therapy, invasive cochlear implants, or other forms of coordinated stimulation to provide a systematic strategy for tinnitus treatment or even a cure.

Long-lasting increase in axonal excitability after epidurally applied DC.

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

Repetitive Acupuncture Point Treatment with Diluted Bee Venom Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced Neuropathic Mice.

UNLABELLED: The chemotherapeutic agent, oxaliplatin, produces a robust painful neuropathy that results in the loss of intraepidermal nerve fibers (IENFs). We have previously reported that an acupuncture point (acupoint) injection of diluted bee venom (DBV) produces a temporary antiallodynic effect in oxaliplatin-induced neuropathic mice. Herein we show a significant long-lasting antinociceptive effect of repetitive DBV acupoint treatment on oxaliplatin-induced mechanical allodynia and a significant reduction in the loss of IENFs. DBV (0.1 mg/kg, subcutaneous) was administered once a day for 18 days beginning on day 15 after oxaliplatin injection. Immunohistochemistry for IENF was performed on the glabrous skin of the hind paw footpad using the pan-neuronal marker, protein gene product 9.5. A temporary increase in mechanical threshold was observed 60 minutes after a single DBV injection into the Zusanli acupoint, and this effect was enhanced over time with repetitive DBV treatments. The basal mechanical threshold before daily DBV injection also increased from day 7 after DBV injections, and peaked at day 14 after DBV treatment. Moreover, the oxaliplatin-induced loss of IENFs was significantly reduced in mice treated repetitively with DBV. Repetitive pretreatment with the α-2 adrenoceptor antagonist, yohimbine, (5 mg/kg, subcutaneous) completely prevented the antiallodynic effects and the increase in IENFs observed in mice treated repetitively with DBV. PERSPECTIVE: We showed that repetitive acupoint stimulation with DBV gradually and significantly reduced oxaliplatin-induced mechanical allodynia and restored the loss of IENFs in neuropathic mice via an α-2 adrenoceptor mechanism. Collectively, results of this study suggest that repetitive acupoint treatment with DBV can be a potential strategy for the management of chemotherapy-induced neuropathy.

Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes.

The purpose of this study was to determine the effect of supplementing the diet of a mouse model of type 2 diabetes with menhaden (fish) oil or daily treatment with resolvin D1 on diabetic neuropathy. The end points evaluated included motor and sensory nerve conduction velocity, thermal sensitivity, innervation of sensory nerves in the cornea and skin, and the retinal ganglion cell complex thickness. Menhaden oil is a natural source for n-3 polyunsaturated fatty acids, which have been shown to have beneficial effects in other diseases. Resolvin D1 is a metabolite of docosahexaenoic acid and is known to have anti-inflammatory and neuroprotective properties. To model type 2 diabetes, mice were fed a high-fat diet for 8 wk followed by a low dosage of streptozotocin. After 8 wk of hyperglycemia, mice in experimental groups were treated for 6 wk with menhaden oil in the diet or daily injections of 1 ng/g body wt resolvin D1. Our findings show that menhaden oil or resolvin D1 did not improve elevated blood glucose, HbA1C, or glucose utilization. Untreated diabetic mice were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities, had decreased innervation of the cornea and skin, and had thinner retinal ganglion cell complex. These end points were significantly improved with menhaden oil or resolvin D1 treatment. Exogenously, resolvin D1 stimulated neurite outgrowth from primary cultures of dorsal root ganglion neurons from normal mice. These studies suggest that n-3 polyunsaturated fatty acids derived from fish oil could be an effective treatment for diabetic neuropathy.

Changes in peptidergic fiber density in the synovium of mice with collagenase-induced acute arthritis.

The effect of acute osteoarthritis (OA) on peripheral nerve fibers (NFs) in synovial tissue, and their association with histological changes were investigated in collagenase-induced OA mice. Collagenase (10 U in 5 µL saline) was injected into the right knee, and the same volume of saline was injected into the left knee as the control. Mice were sacrificed 1, 2, 3, and 4 weeks after the collagenase injection. Histopathological changes in the knee joints were evaluated. The numbers of protein gene product (PGP) 9.5-, calcitonin-gene-related peptide (CGRP)-, and substance P (SP)-positive NFs in the synovial tissue were determined, and their densities in the tissue were calculated. The densities of PGP 9.5- and CGRP-positive NFs in the synovium were drastically decreased 1 week after the collagenase injection. However, by week 4, the density of PGP 9.5- and CGRP-positive NFs had recovered to 84% and 79% of their normal levels, respectively. Despite the poor correlation between the synovitis score and the density of CGRP- or SP-positive NFs in the synovium, the ossification rate of chondrophytes in chondro/osteophyte lesions correlated strongly with the density of CGRP-positive NFs (R = 0.855). These results suggest that the ossification of chondrophytes occurred in parallel with the increase in CGRP-positive fiber density in the synovium during the acute phase of collagenase-induced OA.

Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

Patterns of subsequent progression of localized retinal nerve fiber layer defects on red-free fundus photographs in normal-tension glaucoma.

PURPOSE: To investigate patterns of subsequent progression of localized retinal nerve fiber layer (RNFL) defects and to quantify the extent of progression in normal-tension glaucoma (NTG) patients. METHODS: Thirty-three eyes of 33 consecutive NTG patients who had shown continuous progression of localized RNFL defect on serial red-free fundus photographs were selected for the study. Patterns of subsequent progression of localized RNFL defects were categorized, and extents of progression were quantified. Serial evaluations of disc stereophotographs and visual fields were also performed to detect progression. RESULTS: The most common pattern was continuous widening of the defect towards the macula (n = 11, 33.3%) followed by sharpening of the defect border after widening of the defect towards the macula (n = 5, 15.2%), continuous widening of the defect away from the macula (n = 2, 6.1%), and deepening of the defect after appearance of a new defect (n = 2, 6.1%). Four eyes (12.1%) simultaneously showed two patterns of subsequent progression. In 13 eyes that showed continuous widening of the defect, subsequent angular widening towards the macula and away from the macula were 9.2 ± 6.0° (range, 1.1° to 24.4°; n = 11) and 5.2 ± 4.9° (range, 0.3° to 11.3°; n = 2), respectively. Thirty-two eyes showed no progression of optic disc cupping. Out of the 21 eyes in which Humphrey central 30-2 threshold visual field tests were performed after progression of RNFL defects, 15 eyes showed no deterioration in the visual field. CONCLUSIONS: There were nine patterns of subsequent progression of localized RNFL defects. Among them, continuous RNFL loss proceeding temporally was the most common one. Initial progression of the defect proceeded temporally, especially in the defect located at the inferior fundus, might be at a risk of further RNFL loss temporally.

Patterns of Subsequent Progression of Localized Retinal Nerve Fiber Layer Defects on Red-free Fundus Photographs in Normal-tension Glaucoma

PURPOSE: To investigate patterns of subsequent progression of localized retinal nerve fiber layer (RNFL) defects and to quantify the extent of progression in normal-tension glaucoma (NTG) patients. METHODS: Thirty-three eyes of 33 consecutive NTG patients who had shown continuous progression of localized RNFL defect on serial red-free fundus photographs were selected for the study. Patterns of subsequent progression of localized RNFL defects were categorized, and extents of progression were quantified. Serial evaluations of disc stereophotographs and visual fields were also performed to detect progression. RESULTS: The most common pattern was continuous widening of the defect towards the macula (n = 11, 33.3%) followed by sharpening of the defect border after widening of the defect towards the macula (n = 5, 15.2%), continuous widening of the defect away from the macula (n = 2, 6.1%), and deepening of the defect after appearance of a new defect (n = 2, 6.1%). Four eyes (12.1%) simultaneously showed two patterns of subsequent progression. In 13 eyes that showed continuous widening of the defect, subsequent angular widening towards the macula and away from the macula were 9.2 ± 6.0degrees (range, 1.1degrees to 24.4degrees; n = 11) and 5.2 ± 4.9degrees (range, 0.3degrees to 11.3degrees; n = 2), respectively. Thirty-two eyes showed no progression of optic disc cupping. Out of the 21 eyes in which Humphrey central 30-2 threshold visual field tests were performed after progression of RNFL defects, 15 eyes showed no deterioration in the visual field. CONCLUSIONS: There were nine patterns of subsequent progression of localized RNFL defects. Among them, continuous RNFL loss proceeding temporally was the most common one. Initial progression of the defect proceeded temporally, especially in the defect located at the inferior fundus, might be at a risk of further RNFL loss temporally.

"Clinical Observation on Treatment of Infantile Brachia Plexus Injuries with ""Three Therapies of Clearing the Meridians""" / 针灸推拿医学（英文版）

To observe the clinical efficacy of treatment of infantile brachia plexus injuries with three cooperative therapies of Tuina, Acupuncture and Acupoint injection, which have the function of clearing the meridians. Methods: The affected neck and arm were relaxed with Tuina techniques of one-thumb meditation, grasping and kneading. The points of Jiaji (Ex-B 2) on the neck, Jianjing (GB 21), Futu (LI 18), Jiquan (HT 1), Jianyu (LI 15), Quchi (LI 11), ect were pressed with one thumb. The points of Jiaji (Ex-B 2) on the neck, Tianchuang (SI 16), Futu (LI 18), Jiquan (HT 1), Quchi (LI 11), Waiguan (TE 5), Yangchi (TE 4), Hegu (LI 4)and the corresponding points were inserted with filiform needles and reinforcing-reducing method. The points of Jianyu (LI 15), Jianliao (TE 14), Quchi (LI 11), Shousanli (LI 10),Waiguan (TE 5), Yangchi (TE 4), Hegu (LI 4) were injected with Methylcobalamin injection.The treatment was given once every other day. Results: Of 35 cases, 22 cases were cured, 9 cases greatly improved and 4 cases improved. Conclusion: Three Therapies of Clearing Meridians have a good clinical efficacy for treating infantile brachia plexus injuries.

Treatment of Brachial Plexus Injury by Exterior- and Interior Meridian Acupoints / 针灸推拿医学（英文版）

Exterior-and interior-meridian acupoints were used, mainly by selection of local acupoints along meridian. According to the state of disease, electroacupuncture and acupoint injection were combined to treat brachial plexus injury. Among 12 patients, 6 cases were basically cured, 4 cases got effectiveness and 2 cases had no effectiveness. The therapeutic effect of exterior- and interior-meridian acupoints in brachial plexus injury was satisfactory.

Effect of Electro-Acupuncture on S-100 Protein Expression of Nerve Fibers in the Repair Process of Transected Sciatic Nerve in Rats / 针灸推拿医学（英文版）

Objective: To observe the effects of electro-acupuncture on S-100 protein expression of nerve fibers on the regeneration process of transected sciatic nerve of rats, so as to explore the partial mechanism of electro-acupuncture treatment for peripheral nerve injury.Methods: Following rat's sciatic nerve transection, the nerve regeneration chamber model was established, then the rat was given electro-acupuncture stimulation at the frequency of 5 Hz and frequency of 100 Hz, and the immunohistochemical staining method and image analyzing semi-quantitative technique were adopted to determine the percentage of S-100 protein area,hence to observethe effect of electro-acupuncture on the repair process of transected sciatic nerve of rat and the S-100 protein expression. Results: Electro-acupuncture could significantly potentiate the S-100 protein expression of Schwann Cells (SC) in the repair process of transected sciatic nerve. At the 14th week, 17th week and 20th week after operation, the percentages of S-100 protein area were more obviously increased in 5 Hz electro-acupuncture group and 100 Hz electro-acupuncture group than in model group, with significant differences (P＜0.05). Especially, the better effect was obtained in 5 Hz electro-acupuncture group. Judging from the dynamic treatment, it is very vital to be treated early. Conclusion: Electro-acupuncture is an effective method for the treatment of peripheral nerve injury, and its therapeutic effect is related to the improvement of SC proliferation.

Treatment of 150 Cases of Infantile Brachial Plexus Injury by Tuina / 针灸推拿医学（英文版）

The author selected the acupoints Fengfu (GV 16), Fengchi (GB 20), Hegu (LI 4),Jianjing (GB 21), and adopted manual techniques such as Yizhichan-Thumb waving pressing,An-pressing, Rou-stationary circular pressing, Nie-pinching, Nian-finger twisting, Na-holding,Yao-rotation and Cuo-palm twisting to warm and dredge meridians and collaterals, promote the circulation of qi and blood, and lubricate the joints, to treat 150 cases of infantile brachial plexus injury. The total effective rate was 99.3%.