Progressive axonal dysfunction precedes development of neuropathy in type 2 Diabetes.

To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0-1 [n = 35]), grade 1 (TNS 2-8 [n = 42]), and grade 2/3 (TNS 9-24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction

Nanocluster-Based Ultralow-Temperature Driven Oxide Gate Dielectrics for High-Performance Organic Electronic Devices.

The development of novel dielectric materials with reliable dielectric properties and low-temperature processibility is crucial to manufacturing flexible and high-performance organic thin-film transistors (OTFTs) for next-generation roll-to-roll organic electronics. Here, we investigate the solution-based fabrication of high-k aluminum oxide (Al2O3) thin films for high-performance OTFTs. Nanocluster-based Al2O3 films fabricated by highly energetic photochemical activation, which allows low-temperature processing, are compared to the conventional nitrate-based Al2O3 films. A wide array of spectroscopic and surface analyses show that ultralow-temperature photochemical activation (6 MV/cm). Using this dielectric layer, precisely aligned microrod-shaped 2,7-dioctyl[1]benzothieno [3,2-b][1] benzothiophene (C8-BTBT) single-crystal OTFTs were fabricated via solvent vapor annealing and photochemical patterning of the sacrificial layer

Magnetic Vortex Core Reversal by Excitation of Spin Waves

Micron-sized magnetic platelets in the flux closed vortex state are characterized by an in-plane curling magnetization and a nanometer-sized perpendicularly magnetized vortex core. Having the simplest non-trivial configuration, these objects are of general interest to micromagnetics and may offer new routes for spintronics applications. Essential progress in the understanding of nonlinear vortex dynamics was achieved when low-field core toggling by excitation of the gyrotropic eigenmode at sub-GHz frequencies was established. At frequencies more than an order of magnitude higher vortex state structures possess spin wave eigenmodes arising from the magneto-static interaction. Here we demonstrate experimentally that the unidirectional vortex core reversal process also occurs when such azimuthal modes are excited. These results are confirmed by micromagnetic simulations which clearly show the selection rules for this novel reversal mechanism. Our analysis reveals that for spin wave excitation the concept of a critical velocity as the switching condition has to be modified.Comment: Minor corrections and polishing of previous versio

Development and consensus process for a clinical pathway for the assessment and management of chemotherapy-induced peripheral neuropathy

Background: Cancer patients treated with neurotoxic chemotherapy are at risk of developing neurological symptoms that can impact functional capacity and quality of life. However, there are no standardised pathways to assess and manage chemotherapy-induced peripheral neurotoxicity (CIPN). This study aimed to determine consensus on statements regarding a CIPN assessment and management clinical pathway. Methods: A CIPN clinical pathway (CIPN-path) was developed and reviewed by an expert multi-disciplinary panel and consumers. Agreement with 18 statements regarding four content themes (pretreatment review, screening and assessment, management and referral, and CIPN-path feasibility) were assessed by 70 Australian respondents (68 health professionals, 2 consumers), using a 2-stage Delphi survey process to reach consensus. Respondents rated statements using a 5-point Likert scale to determine the level of agreement, with consensus defined as ≥ 80% of respondents agreeing with each statement. Results: The consensus was reached for 14 of 18 items after stage 1 and all items after stage 2. Feedback was obtained for all items to refine the CIPN-path. There was an agreement on important characteristics of the CIPN-path, including pretreatment screening, regular patient-reported assessment, and a stepped-care approach to investigating and managing symptom burden. There was a lack of agreement on who should oversee CIPN assessment, which may differ according to the structure and resources of each site. Conclusions: There was an overall agreement concerning the CIPN-path to assess and manage CIPN, which may be adapted accordingly to the resources of each clinic. The CIPN-path may assist teams across different health services in identifying CIPN symptoms, aiding decision-making, and reducing morbidity from CIPN

Tracking small sensory nerve action potentials in human axonal excitability studies

BACKGROUND: Excitability studies on normal and diseased human axons in vivo have been greatly enhanced by fast non-invasive threshold-tracking techniques, using surface stimulation and recording. Although sensory axons are often more affected in disease, most studies to date have focussed on motor axons, because of technical difficulties in resolving pathologically small nerve volleys in the presence of noise and stimulus artefact. NEW METHODS: This paper describes techniques for tracking low-amplitude compound action potentials, using a battery-powered, isolated preamplifier of simple construction with high common mode rejection (>125 dB [balanced inputs]) and low noise (<0.4 μV referred to inputs [shorted]). RESULTS: We demonstrate the preamplifier's capability by tracking targets as small as 2 μV for a full range of excitability measurements without the usual distortion due to residual stimulus artefact and without the need for clamping, additional filtering or ensemble averaging. COMPARISON WITH EXISTING METHODS: In practice, threshold-tracking studies have been unable to study sensory axons when the maximal compound sensory action potential was less than about 15 μV. The techniques and amplifier in the present study allow measurements to be made from nerve with maximal responses less than half that size, and we present three recordings in patients with pathologically small nerve action potentials ≤7 μV. CONCLUSIONS: Based on measurements of stimulus artefact distortion, noise and the performance in experiments, we conclude that the techniques described here will facilitate the study of diseased axons for which the sensory potentials have high thresholds and may be only a few microvolts in amplitude

Charge density mismatch synthesis of MEI- and BPH-type zeolites in the TEA+–TMA+–Li+–Sr2+ mixed-structure-directing agent system

Nanocrystalline MEI- and BPH-type zeolites, denoted as PST-11 and PST-12, respectively, have been synthesized using both tetraethylammonium and tetramethylammonium ions, the two simplest alkyl-ammonium species, in the presence of Li+ and Sr2+. PST-12 formation is the first example of a combination of forced and multiple cooperative structure-directions in the charge density mismatch synthesis of zeolites.open1166sciescopu

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function

Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research