ResearchPad - nerves https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Automatic three-dimensional reconstruction of fascicles in peripheral nerves from histological images]]> https://www.researchpad.co/article/elastic_article_14591 Computational studies can be used to support the development of peripheral nerve interfaces, but currently use simplified models of nerve anatomy, which may impact the applicability of simulation results. To better quantify and model neural anatomy across the population, we have developed an algorithm to automatically reconstruct accurate peripheral nerve models from histological cross-sections. We acquired serial median nerve cross-sections from human cadaveric samples, staining one set with hematoxylin and eosin (H&E) and the other using immunohistochemistry (IHC) with anti-neurofilament antibody. We developed a four-step processing pipeline involving registration, fascicle detection, segmentation, and reconstruction. We compared the output of each step to manual ground truths, and additionally compared the final models to commonly used extrusions, via intersection-over-union (IOU). Fascicle detection and segmentation required the use of a neural network and active contours in H&E-stained images, but only simple image processing methods for IHC-stained images. Reconstruction achieved an IOU of 0.42±0.07 for H&E and 0.37±0.16 for IHC images, with errors partially attributable to global misalignment at the registration step, rather than poor reconstruction. This work provides a quantitative baseline for fully automatic construction of peripheral nerve models. Our models provided fascicular shape and branching information that would be lost via extrusion.

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<![CDATA[The braincase of Malawisaurus dixeyi (Sauropoda: Titanosauria): A 3D reconstruction of the brain endocast and inner ear]]> https://www.researchpad.co/article/5c6dca27d5eed0c48452a84d

A braincase of the Cretaceous titanosaurian sauropod Malawisaurus dixeyi, complete except for the olfactory region, was CT scanned and a 3D rendering of the endocast and inner ear was generated. Cranial nerves appear in the same configuration as in other sauropods, including derived features that appear to characterize titanosaurians, specifically, an abducens nerve canal that passes lateral to the pituitary fossa rather than entering it. Furthermore, the hypoglossal nerve exits the skull via a single foramen, consistent with most titanosaurians, while other saurischians, including the basal titanosauriform, Giraffatitan, contain multiple rootlets. The size of the vestibular labyrinth is smaller than in Giraffatitan, but larger than in most derived titanosaurians. Similar to the condition found in Giraffatitan, the anterior semicircular canal is larger than the posterior semicircular canal. This contrasts with more derived titanosaurians that contain similarly sized anterior and posterior semicircular canals, congruent with the interpretation of Malawisaurus as a basal titanosaurian. Measurements of the humerus of Malawisaurus provide a body mass estimate of 4.7 metric tons. Comparison of body mass to radius of the semicircular canals of the vestibular labyrinth reveals that Malawisaurus fits the allometric relationship found in previous studies of extant mammals and Giraffatitan brancai. As in Giraffatitan, the anterior semicircular canal is significantly larger than is predicted by the allometric relationship suggesting greater sensitivity and slower movement of the head in the sagittal plane.

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<![CDATA[Does appreciative inquiry decrease false positive diagnosis during leprosy case detection campaigns in Bihar, India? An operational research study]]> https://www.researchpad.co/article/5c269765d5eed0c48470f692

Background

India contributes ~60% to the global leprosy burden. The country implements 14-day community-based leprosy case detection campaigns (LCDC) periodically in all high endemic states. Paramedical staff screen the population and medical officers of primary health centres (PHCs) diagnose and treat leprosy cases. Several new cases were detected during the two LCDCs held in September-2016 and February-2018. Following these LCDCs, a validation exercise was conducted in 8 Primary health centres (PHCs) of 4 districts in Bihar State by an independent expert group, to assess the correctness of case diagnosis. Just before the February 2018 LCDC campaign, we conducted an “appreciative inquiry” (AI) involving the health care staff of these 8 PHCs using the 4-D framework (Discovery-Dream-Design-Destiny).

Objectives

To assess whether the incorrect case diagnosis (false positive diagnosis) reduced as a result of AI in the 8 PHCs between the two LCDC conducted in September-2016 and February-2018.

Methodology/principal findings

A three-phase quantitative-qualitative-quantitative mixed methods research (embedded design) with the two validation exercises conducted following September-2016 and February-2018 LCDCs as quantitative phases and AI as qualitative phase. In September-2016 LCDC, 303 new leprosy cases were detected, of which 196 cases were validated and 58 (29.6%) were false positive diagnosis. In February-2018 LCDC, 118 new leprosy cases were detected of which 96 cases were validated and 22 cases (23.4%) were false positive diagnosis. After adjusting for the age, gender, type of cases and individual PHCs fixed effects, the proportion of false positive diagnosis reduced by -9% [95% confidence intervals (95%CI): -20.2% to 1.7%, p = 0.068]

Conclusion

False positive diagnosis is a major issue during LCDCs. Though the decline in false positive diagnosis is not statistically significant, the findings are encouraging and indicates that appreciative inquiry can be used to address this deficiency in programme implementation.

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<![CDATA[Growth factors expression and ultrastructural morphology after application of low-level laser and natural latex protein on a sciatic nerve crush-type injury]]> https://www.researchpad.co/article/5c3fa5aad5eed0c484ca713c

The effects of low-level laser therapy (LLLT) and natural latex protein (F1, Hevea brasiliensis) were evaluated on crush-type injuries (15kg) to the sciatic nerve in the expressions of nerve growth factor (NGF) and vascular endothelium growth factor (VEGF) and ultrastructural morphology to associate with previous morphometric data using the same protocol of injury and treatment. Thirty-six male rats were allocated into six experimental groups (n = 6): 1-Control; 2-Exposed nerve; 3-Injured nerve; 4-LLLT (15J/cm2, 780nm, 30mW, Continuous Wave) treated injured nerve; 5-F1 (0,1mg) treated injured nerve; and 6-LLLT&F1 treated injured nerve. Four or eight weeks after, sciatic nerve samples were processed for analysis. NGF expression were higher (p<0.05) four weeks after in all injured groups in comparison to Control (Med:0.8; Q1:0; Q3:55.5%area). Among them, the Injured (Med:70.7; Q1:64.4; Q3:77.5%area) showed the highest expression, and F1 (Med:17.3; Q1:14.1; Q3:21.7%area) had the lowest. At week 8, NGF expressions decreased in the injured groups. VEGF was expressed in all groups; its higher expression was observed in the injured groups 4 weeks after (Injured. Med:29.5; F1. Med:17.7 and LLLT&F1. Med:19.4%area). At week 8, a general reduction of VEGF expression was noted, remaining higher in F1 (Med:35.1; Q1.30.6; Q3.39.6%area) and LLLT&F1 (Med:18.5; Q1:16; Q3:25%area). Ultrastructural morphology revealed improvements in the treated groups; 4 weeks after, the F1 group presented greater quantity and diameter of the nerve fibers uniformly distributed. Eight weeks after, the F1 and LLLT&F1 showed similar characteristics to the non-injured groups. In summary, these results and our previous studies indicated that F1 and LLLT may favorably influence the healing of nerve crush injury. Four weeks after nerve injury F1 group showed the best results suggesting recovery acceleration; at 8th week F1 and LLLT&F1 groups presented better features and higher vascularization that could be associated with VEGF maintenance.

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<![CDATA[The neuroanatomy of the siboglinid Riftia pachyptila highlights sedentarian annelid nervous system evolution]]> https://www.researchpad.co/article/5c1c0ab1d5eed0c4844268d5

Tracing the evolution of the siboglinid group, peculiar group of marine gutless annelids, requires the detailed study of the fragmentarily explored central nervous system of vestimentiferans and other siboglinids. 3D reconstructions of the neuroanatomy of Riftia revealed that the “brain” of adult vestimentiferans is a fusion product of the supraesophageal and subesophageal ganglia. The supraesophageal ganglion-like area contains the following neural structures that are homologous to the annelid elements: the peripheral perikarya of the brain lobes, two main transverse commissures, mushroom-like structures, commissural cell cluster, and the circumesophageal connectives with two roots which give rise to the palp neurites. Three pairs of giant perikarya are located in the supraesophageal ganglion, giving rise to the paired giant axons. The circumesophageal connectives run to the VNC. The subesophageal ganglion-like area contains a tripartite ventral aggregation of perikarya (= the postoral ganglion of the VNC) interconnected by the subenteral commissure. The paired VNC is intraepidermal, not ganglionated over most of its length, associated with the ciliary field, and comprises the giant axons. The pairs of VNC and the giant axons fuse posteriorly. Within siboglinids, the vestimentiferans are distinguished by a large and considerably differentiated brain. This reflects the derived development of the tentacle crown. The tentacles of vestimentiferans are homologous to the annelid palps based on their innervation from the dorsal and ventral roots of the circumesophageal connectives. Neuroanatomy of the vestimentiferan brains is close to the brains of Cirratuliiformia and Spionida/Sabellida, which have several transverse commissures, specific position of the giant somata (if any), and palp nerve roots (if any). The palps and palp neurite roots originally developed in all main annelid clades (basally branching, errantian and sedentarian annelids), show the greatest diversity in their number in sedentarian species. Over the course of evolution of Sedentaria, the number of palps and their nerve roots either dramatically increased (as in vestimentiferan siboglinids) or were lost.

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<![CDATA[Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia]]> https://www.researchpad.co/article/5c196696d5eed0c484b52502

In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.

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<![CDATA[Effects of caloric restriction on neuropathic pain, peripheral nerve degeneration and inflammation in normometabolic and autophagy defective prediabetic Ambra1 mice]]> https://www.researchpad.co/article/5c18138bd5eed0c484775367

There is a growing interest on the role of autophagy in diabetes pathophysiology, where development of neuropathy is one of the most frequent comorbidities. We have previously demonstrated that neuropathic pain after nerve damage is exacerbated in autophagy-defective heterozygous Ambra1 mice. Here, we show the existence of a prediabetic state in Ambra1 mice, characterized by hyperglycemia, intolerance to glucose and insulin resistance. Thus, we further investigate the hypothesis that prediabetes may account for the exacerbation of allodynia and chronic pain and that counteracting the autophagy deficit may relieve the neuropathic condition. We took advantage from caloric restriction (CR) able to exert a double action: a powerful increase of autophagy and a control on the metabolic status. We found that CR ameliorates neuropathy throughout anti-inflammatory and metabolic mechanisms both in Ambra1 and in WT animals subjected to nerve injury. Moreover, we discovered that nerve lesion represents, per se, a metabolic stressor and CR reinstates glucose homeostasis, insulin resistance, incomplete fatty acid oxidation and energy metabolism. As autophagy inducer, CR promotes and anticipates Schwann cell autophagy via AMP-activated protein kinase (AMPK) that facilitates remyelination in peripheral nerve. In summary, we provide new evidence for the role of autophagy in glucose metabolism and identify in energy depletion by dietary restriction a therapeutic approach in the fight against neuropathic pain.

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<![CDATA[Topographical study of the trapezius muscle, greater occipital nerve, and occipital artery for facilitating blockade of the greater occipital nerve]]> https://www.researchpad.co/article/5b8acdf140307c144d0de05b

The aim of this study was to clarify the topographical relationships between the greater occipital nerve and the trapezius muscle and between the greater occipital nerve and the occipital artery in the occiput in order to increase the success rate of greater occipital nerve blockade. Fifty-six halved heads of 28 cadavers were used in this study. The piercing points and the courses of the greater occipital nerve and occipital artery were analyzed by dividing a line connecting between the external occipital protuberance and mastoid process into three equal parts. A circle with a radius of 2 cm drawn at the medial trisection point of this line was divided into four equal sectors. The greater occipital nerve simply passed the lateral border of the trapezius muscle and then pierced the fascia connecting the cranial attachment of the trapezius muscle with the sternocleidomastoid muscle in 62.5% of the specimens, whereas it pierced the muscle itself in the other 37.5%. The greater occipital nerve and occipital artery pierced the fascia within the 2-cm-radius circle in 85.7% and 98.2% of the specimens, respectively. The piercing points of the greater occipital nerve and occipital artery were observed most frequently in the inferomedial (42.9%) and inferolateral (37.5%) sectors of the circle, respectively. The greater occipital nerve and occipital artery pierced the same sector of the circle and accompanied each other in 51.8% of the specimens. These results are expected to improve the understanding of the topographical relationships between the greater occipital nerve and trapezius muscle and between the greater occipital nerve and occipital artery in the occiput, and thus provide helpful information for the management of occipital neuralgia.

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<![CDATA[Detection of PrPres in peripheral tissue in pigs with clinical disease induced by intracerebral challenge with sheep-passaged bovine spongiform encephalopathy agent]]> https://www.researchpad.co/article/5b4a1934463d7e428027f895

Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to pigs via intracerebral inoculation. A clear link has been established between the consumption of products of bovine origin contaminated with the BSE agent and the development of variant Creutzfeldt-Jakob disease in humans. Small ruminants can also naturally develop BSE, and sheep-adapted BSE (Sh-BSE) propagates more efficiently than cattle BSE in pigs and in mouse models expressing porcine prion protein. In addition, Sh-BSE shows greater efficiency of transmission to human models than original cow BSE. While infectivity and/or abnormal PrP accumulation have been reported in the central nervous system in BSE-infected pigs, the ability of the agent to replicate in peripheral tissues has not been fully investigated. We previously characterized the presence of prions in a panel of tissues collected at the clinical stage of disease from pigs experimentally infected with Sh-BSE. Western blot revealed low levels of PrPres accumulation in lymphoid tissues, nerves, and skeletal muscles from 4 of the 5 animals analysed. Using protein misfolding cyclic amplification (PMCA), which we found to be 6 log fold more sensitive than direct WB for the detection of pig BSE, we confirmed the presence of the Sh-BSE agent in lymphoid organs, nerves, ileum, and striated muscles from all 5 inoculated pigs. Surprisingly, PrPres positivity was also detected in white blood cells from one pig using this method. The presence of infectivity in lymphoid tissues, striated muscles, and peripheral nerves was confirmed by bioassay in bovine PrP transgenic mice. These results demonstrate the ability of BSE-derived agents to replicate efficiently in various peripheral tissues in pigs. Although no prion transmission has been reported in pigs following oral BSE challenge, our data support the continuation of the Feed Ban measure implemented to prevent entry of the BSE agent into the feed chain.

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<![CDATA[Cranial Anatomy and Palaeoneurology of the Archosaur Riojasuchus tenuisceps from the Los Colorados Formation, La Rioja, Argentina]]> https://www.researchpad.co/article/5989db3bab0ee8fa60bd4fa9

Riojasuchus tenuisceps Bonaparte 1967 is currently known from four specimens, including two complete skulls, collected in the late 1960s from the upper levels of the Los Colorados Formation (Late Triassic), La Rioja, Argentina. Computed tomography (CT) scans of the skulls of the holotype and a referred specimen of Riojasuchus tenuisceps and the repreparation of the latter allows recognition of new features for a detailed analysis of its cranial anatomy and its comparison with a wide variety of other archosauriform taxa. The diagnosis of Riojasuchus tenuisceps is emended and two autapomorphies are identified on the skull: (1) a deep antorbital fossa with its anterior and ventral edges almost coinciding with the same edges of the maxilla itself and (2) a suborbital fenestra equal in size to the palatine-pterygoid fenestra. Also, the first digital 3D reconstruction of the encephalon of Riojasuchus tenuisceps was carried out to study its neuroanatomy, showing a shape and cranial nerve disposition consistent to that of other pseudosuchians.

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<![CDATA[Evaluating Tissue-Specific Recombination in a Pdgfrα-CreERT2 Transgenic Mouse Line]]> https://www.researchpad.co/article/5989d9daab0ee8fa60b6727a

In the central nervous system (CNS) platelet derived growth factor receptor alpha (PDGFRα) is expressed exclusively by oligodendrocyte progenitor cells (OPCs), making the Pdgfrα promoter an ideal tool for directing transgene expression in this cell type. Two Pdgfrα-CreERT2 mouse lines have been generated for this purpose which, when crossed with cre-sensitive reporter mice, allow the temporally restricted labelling of OPCs for lineage-tracing studies. These mice have also been used to achieve the deletion of CNS-specific genes from OPCs. However the ability of Pdgfrα-CreERT2 mice to induce cre-mediated recombination in PDGFRα+ cell populations located outside of the CNS has not been examined. Herein we quantify the proportion of PDGFRα+ cells that become YFP-labelled following Tamoxifen administration to adult Pdgfrα-CreERT2::Rosa26-YFP transgenic mice. We report that the vast majority (>90%) of PDGFRα+ OPCs in the CNS, and a significant proportion of PDGFRα+ stromal cells within the bone marrow (~38%) undergo recombination and become YFP-labelled. However, only a small proportion of the PDGFRα+ cell populations found in the sciatic nerve, adrenal gland, pituitary gland, heart, gastrocnemius muscle, kidney, lung, liver or intestine become YFP-labelled. These data suggest that Pdgfrα-CreERT2 transgenic mice can be used to achieve robust recombination in OPCs, while having a minimal effect on most PDGFRα+ cell populations outside of the CNS.

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<![CDATA[Macrophage-Colony Stimulating Factor Derived from Injured Primary Afferent Induces Proliferation of Spinal Microglia and Neuropathic Pain in Rats]]> https://www.researchpad.co/article/5989d9d3ab0ee8fa60b64e14

Peripheral nerve injury induces proliferation of microglia in the spinal cord, which can contribute to neuropathic pain conditions. However, candidate molecules for proliferation of spinal microglia after injury in rats remain unclear. We focused on the colony-stimulating factors (CSFs) and interleukin-34 (IL-34) that are involved in the proliferation of the mononuclear phagocyte lineage. We examined the expression of mRNAs for macrophage-CSF (M-CSF), granulocyte macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF) and IL-34 in the dorsal root ganglion (DRG) and spinal cord after spared nerve injury (SNI) in rats. RT-PCR and in situ hybridization revealed that M-CSF and IL-34, but not GM- or G-CSF, mRNAs were constitutively expressed in the DRG, and M-CSF robustly increased in injured-DRG neurons. M-CSF receptor mRNA was expressed in naive rats and increased in spinal microglia following SNI. Intrathecal injection of M-CSF receptor inhibitor partially but significantly reversed the proliferation of spinal microglia and in early phase of neuropathic pain induced by SNI. Furthermore, intrathecal injection of recombinant M-CSF induced microglial proliferation and mechanical allodynia. Here, we demonstrate that M-CSF is a candidate molecule derived from primary afferents that induces proliferation of microglia in the spinal cord and leads to induction of neuropathic pain after peripheral nerve injury in rats.

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<![CDATA[The Burden of Leprosy in Cameroon: Fifteen Years into the Post-elimination Era]]> https://www.researchpad.co/article/5989da3bab0ee8fa60b88135

Background

Cameroon achieved the elimination target of leprosy in 2000, and has maintained this status ever since. However, a number of health districts in the country continue to report significant numbers of leprosy cases. The aim of this study was to assess the burden of leprosy in Cameroon from 2000 to 2014.

Methods

We obtained and analysed using the new leprosy burden concept of analysis, leprosy surveillance data collected between 2000 and 2014 from the National Leprosy Control Programme.

Principal findings

Cameroon achieved leprosy elimination in 2000, registering a prevalence rate of 0.94/10,000 population. The prevalence rate dropped further to reach 0.20/10,000 population (78% reduction) in 2014. Similarly, the new case detection rate dropped from 4.88/100,000 population in 2000 to 1.46/100,000 population (85.3% reduction) in 2014. All 10 regions of the country achieved leprosy elimination between 2000 and 2014; however, 10 health districts were still to do so by 2014. The number of high-leprosy-burden regions decreased from 8 in 2000 to 1 in 2014. Seven and two regions were respectively medium and low-burdened at the end of 2014. At the health districts level, 18 remained at the high-leprosy-burdened level in 2014.

Conclusion

The leprosy prevalence and detection rates as well as the overall leprosy burden in Cameroon have dropped significantly between 2000 and 2014. However, a good number of health districts remain high-leprosy-burdened. The National Leprosy Control Programme should focus efforts on these health districts in the next coming years in order to further reduce the burden of leprosy in the country.

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<![CDATA[Expression patterns of Slit and Robo family members in adult mouse spinal cord and peripheral nervous system]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbdd9

The secreted glycoproteins, Slit1-3, are classic axon guidance molecules that act as repulsive cues through their well characterised receptors Robo1-2 to allow precise axon pathfinding and neuronal migration. The expression patterns of Slit1-3 and Robo1-2 have been most characterized in the rodent developing nervous system and the adult brain, but little is known about their expression patterns in the adult rodent peripheral nervous system. Here, we report a detailed expression analysis of Slit1-3 and Robo1-2 in the adult mouse sciatic nerve as well as their expression in the nerve cell bodies within the ventral spinal cord (motor neurons) and dorsal root ganglion (sensory neurons). Our results show that, in the adult mouse peripheral nervous system, Slit1-3 and Robo1-2 are expressed in the cell bodies and axons of both motor and sensory neurons. While Slit1 and Robo2 are only expressed in peripheral axons and their cell bodies, Slit2, Slit3 and Robo1 are also expressed in satellite cells of the dorsal root ganglion, Schwann cells and fibroblasts of peripheral nerves. In addition to these expression patterns, we also demonstrate the expression of Robo1 in blood vessels of the peripheral nerves. Our work gives important new data on the expression patterns of Slit and Robo family members within the peripheral nervous system that may relate both to nerve homeostasis and the reaction of the peripheral nerves to injury.

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<![CDATA[Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality]]> https://www.researchpad.co/article/5989d9f9ab0ee8fa60b7123d

Objective

To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI).

Research Design and Methods

Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration.

Results

Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes.

Conclusions

In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.

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<![CDATA[640-Slice CT Measurement of Superior Orbital Fissure as Gateway for Light into the Brain: Statistical Evaluation of Area and Distance]]> https://www.researchpad.co/article/5989db4bab0ee8fa60bda3ed

Objective

Our aim was to provide normative data concerning superior orbital fissure area (SOFA), ocular skin and the substantia nigra (D-SS) and orbital fissure and the substantia nigra (D-SOF-S) distances by CT scan in adult Caucasian population

Methods

The area of the superior orbital fissure (SOF), the distance between the ocular skin and the substantia nigra and the distance between the superior orbital fissure and the substantia nigra using CT and 3D-CT images.

Results

Normative data stratified for age and gender were obtained. The data here reported show that some degree of variability in SOFA, D-SS and D-SOF-S measurements can be observed healthy Caucasian subjects. Gender stratified prediction intervals (mean +/- 2 Standard Deviations) for SOFA and D-SOF-S were 69.2 (+/-15.8) and 38.4 (+/-7.6) for male and 56.8 (+/-11.9) and 36.5 (+/-6.1) for female, respectively. Age and gender significantly impacted on D-SS values and normative data were constructed generating data stratified for these two variables. D-SS was 89.4 (+/-10.3) and 86.4 (+/-9.7) for male and female, respectively.

Conclusions

Here we provide adjunctive anatomical information on specific anatomical cerebral zones. Our data may have implications for surgeons actively committed to treat pathological conditions involving these cerebral areas. Additionally, the anatomical variability found with respect to SOF and the potential different exposure of the substanzia nigra to the bright light could play a role in Parkinson’s disease as already speculated in literature.

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<![CDATA[Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury]]> https://www.researchpad.co/article/5989daf0ab0ee8fa60bc0ef7

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.

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<![CDATA[Postoperative pain treatment after total knee arthroplasty: A systematic review]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbd36

Introduction

The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA).

Methods

This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis.

Results

The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low.

Conclusion

A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA.

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<![CDATA[Deficiency of adaptive immunity does not interfere with Wallerian degeneration]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf55d

Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.

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<![CDATA[Temporal Analysis of Gene Expression in the Murine Schwann Cell Lineage and the Acutely Injured Postnatal Nerve]]> https://www.researchpad.co/article/5989da52ab0ee8fa60b8e0e9

Schwann cells (SCs) arise from neural crest cells (NCCs) that first give rise to SC precursors (SCPs), followed by immature SCs, pro-myelinating SCs, and finally, non-myelinating or myelinating SCs. After nerve injury, mature SCs ‘de-differentiate’, downregulating their myelination program while transiently re-activating early glial lineage genes. To better understand molecular parallels between developing and de-differentiated SCs, we characterized the expression profiles of a panel of 12 transcription factors from the onset of NCC migration through postnatal stages, as well as after acute nerve injury. Using Sox10 as a pan-glial marker in co-expression studies, the earliest transcription factors expressed in E9.0 Sox10+ NCCs were Sox9, Pax3, AP2α and Nfatc4. E10.5 Sox10+ NCCs coalescing in the dorsal root ganglia differed slightly, expressing Sox9, Pax3, AP2α and Etv5. E12.5 SCPs continued to express Sox10, Sox9, AP2α and Pax3, as well as initiating Sox2 and Egr1 expression. E14.5 immature SCs were similar to SCPs, except that they lost Pax3 expression. By E18.5, AP2α, Sox2 and Egr1 expression was turned off in the nerve, while Jun, Oct6 and Yy1 expression was initiated in pro-myelinating Sox9+/Sox10+ SCs. Early postnatal and adult SCs continued to express Sox9, Jun, Oct6 and Yy1 and initiated Nfatc4 and Egr2 expression. Notably, at all stages, expression of each marker was observed only in a subset of Sox10+ SCs, highlighting the heterogeneity of the SC pool. Following acute nerve injury, Egr1, Jun, Oct6, and Sox2 expression was upregulated, Egr2 expression was downregulated, while Sox9, Yy1, and Nfatc4 expression was maintained at similar frequencies. Notably, de-differentiated SCs in the injured nerve did not display a transcription factor profile corresponding to a specific stage in the SC lineage. Taken together, we demonstrate that uninjured and injured SCs are heterogeneous and distinct from one another, and de-differentiation recapitulates transcriptional aspects of several different embryonic stages.

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