Three-dimensional microscopy provides more extended depth of penetration compared with conventional light microscopy and is known to be useful in clinical evaluation of thick biological specimens. ...Skin nerve biopsy together with the quantification of intraepidermal nerve fibers in multiple thick sections has been widely adopted for evaluating peripheral neuropathies. The aim of the present study was to evaluate the effectivity of three-dimensional microscopy in reducing the required time and inter-rater discrepancies, especially in the case of personnel not familiar with the quantification methods. A total of six cryo-sectioned specimens were analyzed for the study and the skin samples were collected from one patient with postherpetic neuralgia who voluntarily participated in the study. Two investigators, a physician and non-physician assessed the intraepidermal nerve fiber densities and required analysis time using three different methods including direct visualization of tissue slides, and analysis with two- and three-dimensional images. Three-dimensional microscopy could produce images that enabled reliable evaluation of intraepidermal nerve fibers; the accuracy of analysis was statistically comparable between the physician and non-physician (p > .05). Three-dimensional microscopy also enabled the non-physician to proceed meaningfully faster evaluation compared with the direct visualization method (p = .03). Three-dimensional microscopy could be one of the useful methods to improve accuracy and convenience of the analysis of intraepidermal nerve fibers especially appropriate for unaccustomed physician or non-physician. RESEARCH HIGHLIGHTS: Three-dimensional microscopy is capable of producing images with more extended depth of penetration compared with conventional light microscopy and has been known to be suitable for clinical evaluation of thick biological specimens. Cutaneous nerve biopsy and the quantification of nerve fibers in thick sections has been widely adopted for evaluating peripheral neuropathies. Three-dimensional microscopy could be especially appropriate for unaccustomed physician or non-physician to improve accuracy and convenience of the analysis of intraepidermal nerve fibers.
Abstract
Three-dimensional (3-D) analysis of intraepidermal nerve fibers (IENFs) is conducted to advance assessment methods for peripheral neuropathies and pruritic skin disorders. The skin-clearing ...technique was proven to be a reliable method for 3-D imaging of IENFs. Nonetheless, it still requires further improvement in the imaging process. The aim of this study was to standardize the 3-D evaluation method of IENFs and to suggest promising 3-D biomarkers for clinical application. A total of nine healthy individuals were prospectively enrolled. The newly adopted suction blister method was combined with the tissue-clearing technique. The detailed structure of the IENFs was reconstructed and quantified using the neuron tracing software. The suction blister method showed improved linear integrity of IENFs compared with those obtained from the previously used salt-split skin test. The 3-D parameters most significantly related to natural aging were the convex hull two-dimensional perimeter and the total length (both
p
= 0.020). The meaningful correlations were followed by total volume (
p
= 0.025), ends (
p
= 0.026), convex hull 3-D surface, and complexity (both
p
= 0.030). Thus, the 3-D parameters could be utilized as possible biomarkers to identify ambiguous pathologies of peripheral neuropathies and pruritic skin disorders.
The properties of cement mortars containing added nano-SiO2 were experimentally studied. The amorphous or glassy silica, which is the major component of a pozzolan, reacts with calcium hydroxide ...formed from calcium silicate hydration. The rate of the pozzolanic reaction is proportional to the amount of surface area available for reaction. Therefore, it is plausible to add nano-SiO2 particles in order to make high-performance concrete. The results show that the compressive strengths of mortars with nano-SiO2 particles were all higher than those of mortars containing silica fume at 7 and 28 days. It is shown that the nano-particles are more effective for enhancing strength than silica fume. In addition, the continuous hydration progress was monitored by SEM observation, by examining the residual quantity of Ca(OH)2 and the rate of heat evolution. The results indicate that nano-scale SiO2 behaves not only as a filler to improve microstructure, but also as an activator to promote pozzolanic reaction. 4 refs.
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•W based thermo-electrochemical cell with hexacynaoferrate electrolyte.•Combination the redox reaction of the electrolyte and the oxidation reaction of W electrodes.•Maximum Seebeck ...coefficient of 1.66 mV K−1 and maximum power density of 425 mW m−2 using non-noble metal electrodes.
Thermo-electrochemical cells utilizing aqueous hexacyanoferrate electrolytes are recognized as an effective energy harvesting system for low-grade waste heat (≤170 °C) owing to their high stability and simple design. Nevertheless, the power generation of thermo-electrochemical cells is low due to the Seebeck coefficient of hexacyanoferrate electrolyte. Herein, we propose hybrid thermo-electrochemical cells using tungsten electrodes, exploiting the redox reaction of hexacyanoferrate and oxidation of the tungsten electrode. Enhanced Seebeck coefficient was attributed to the combination of the two reactions: the redox reaction of the electrolyte and oxidation reaction of tungsten electrodes. The developed tungsten electrode-based hybrid thermo-electrochemical cells generated a Seebeck coefficient of 1.66 mV K−1 and 425 mW m−2 at a dT of 50 °C, ~ 70% higher the power output of platinum and carbon electrodes. From an economic viewpoint, the cost of tungsten makes up for its inevitable consumption due to dissolution and the cost of periodic electrode replacement. Our system is an innovative solution, which might contribute to the commercialization of thermo-electrochemical cells.
•Shear wave elastography (SWE) and high-definition (HD) color provide useful supportive information for the evaluation of carpal tunnel syndrome (CTS).•SWE discriminated CTS severity, and detected ...CTS patients with normal nerve conduction study results.•50.12-kPa for median nerve (MN) stiffness at the wrist and 1.91 for the MN stiffness ratio are cutoff values for CTS diagnosis.
The diagnostic values of measuring median nerve (MN) stiffness and vascularity with shear wave elastography (SWE) and high-definition (HD) color were investigated in carpal tunnel syndrome (CTS).
Seventy patients (123 wrists) with CTS and thirty-five healthy volunteers (70 wrists) were enrolled. Based on nerve conduction studies (NCS), the patients were subdivided into NCS-negative, mild-to-moderate, and severe CTS groups. MN and abductor pollicis brevis (APB) SWE and MN HD color were performed on a longitudinal plane.
The mild-to-moderate and severe CTS groups showed increased MN stiffness at the wrist and MN stiffness ratio (wrist-to forearm) compared with the control (p < 0.001). The NCS-negative CTS group showed increased MN stiffness at the wrist (p = 0.022) and MN stiffness ratio (p = 0.032) compared with the control. The severe CTS group showed increased MN stiffness at the wrist compared with the mild-to-moderate CTS group (p = 0.034). The cutoff-values in diagnosing NCS-confirmed CTS were 50.12 kPa for MN stiffness at the wrist, 1.91 for MN stiffness ratio, and grade 1 for HD color.
SWE and HD color are good supportive tools in diagnosing and assessing severity in CTS.
SWE and HD color demonstrated that MN in CTS was associated with increased stiffness and hypervascularity.
We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the ...central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell–based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.
A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 ...months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.
ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months.
Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.
ClinicalTrials.gov NCT04745299 . Registered on Feb 9, 2021. Clinical Research Information Service (CRIS) KCT0005954 . Registered on Mar 4, 2021.
Production of lactic acid from renewable sugars has received growing attention as lactic acid can be used for making renewable and bio-based plastics. However, most prior studies have focused on ...production of lactic acid from glucose despite that cellulosic hydrolysates contain xylose as well as glucose. Microbial strains capable of fermenting both glucose and xylose into lactic acid are needed for sustainable and economic lactic acid production. In this study, we introduced a lactic acid-producing pathway into an engineered Saccharomyces cerevisiae capable of fermenting xylose. Specifically, ldhA from the fungi Rhizopus oryzae was overexpressed under the control of the PGK1 promoter through integration of the expression cassette in the chromosome. The resulting strain exhibited a high lactate dehydrogenase activity and produced lactic acid from glucose or xylose. Interestingly, we observed that the engineered strain exhibited substrate-dependent product formation. When the engineered yeast was cultured on glucose, the major fermentation product was ethanol while lactic acid was a minor product. In contrast, the engineered yeast produced lactic acid almost exclusively when cultured on xylose under oxygen-limited conditions. The yields of ethanol and lactic acid from glucose were 0.31 g ethanol/g glucose and 0.22 g lactic acid/g glucose, respectively. On xylose, the yields of ethanol and lactic acid were <0.01 g ethanol/g xylose and 0.69 g lactic acid/g xylose, respectively. These results demonstrate that lactic acid can be produced from xylose with a high yield by S. cerevisiae without deleting pyruvate decarboxylase, and the formation patterns of fermentations can be altered by substrates.
The results of video head impulse tests (video-HITs) may be confounded by data artifacts of various origins, including pupil size and eyelid obstruction of the pupil. This study aimed to determine ...the effect of these factors on the results of video-HITs. We simulated ptosis by adopting pharmacological dilatation of the pupil in 21 healthy participants (11 women; age 24–58 years). Each participant underwent video-HITs before and after pupillary dilatation using 0.5% tropicamide. We assessed the changes in the vestibulo-ocular reflex (VOR) gain, corrective saccade amplitude, and frequency of eyelid flicks. After pupillary dilatation, the VOR gain decreased for both right (RAC; 1.12
±
0.12 vs. 1.01
±
0.16,
p
= 0.011) and left anterior canals (LACs; 1.15
±
0.13 vs. 0.96
±
0.14,
p
< 0.001), and right posterior canal (RPC, 1.10
±
0.13 vs. 0.98
±
0.09,
p
= 0.001). The corrective saccade amplitudes also decreased significantly for all four vertical canals. The frequency of eyelid flicks, however, did not change. The changes of VOR gain were positively correlated with the lid excursion in RPC (
r
= 0.629,
p
= 0.002) and LPC (
r
= 0.549,
p
= 0.010). Our study indicates that eyelid position and pupil size should be considered when interpreting the results of video-HITs, especially for the vertical canals. Pupils should be shrunk in a very well-lit room, and artifacts should be prevented by taping or lifting the eyelids as required during video-HITs.
