Total saponin extract, ginsenoside Rb1, and compound K alleviate peripheral and central neuropathic pain through estrogen receptors on rats.

In this study, we investigated whether total saponin extract (TSE), ginsenoside Rb1, and Rb1 metabolite compound K, which are isolated from red ginseng, have antinociceptive effects on peripheral and central neuropathic pain (PNP and CNP, respectively). PNP and CNP were induced by tail nerve injury (TNI) at S1 and by contusive spinal cord injury (SCI) at T9 in male Sprague-Dawley rats, respectively. Two weeks after TNI or 4 weeks after SCI, pain-induced rats were orally administered vehicle, TSE (50 mg/kg), Rb1 (12.5 mg/kg), compound K (7 mg/kg), or gabapentin (GBP, 60 mg/kg), and the antinociceptive effects were examined by von Frey filament, cold/warm water, and hot plate analyses. Allodynia and hyperalgesia were significantly alleviated by TSE, Rb1, and GBP 1 hr after drug administration. The immunohistochemistry and real-time RT-PCR results showed that the activation of microglia/astrocytes and the expression of inflammatory mediators such as Il-1ß, Il-6, iNOS, and Cox-2 were also significantly inhibited in L4-L5 spinal cord of CNP-induced rats 1 hr after drug administration. Furthermore, the antinociceptive effects of TSE and Rb1 were reversed by treatment with the estrogen receptor (ER) antagonist ICI182780. In particular, compound K also significantly alleviated both PNP and CNP. Therefore, our results indicate that TSE, Rb1, and compound K have potential antinociceptive effects against neuropathic pain that might be mediated through the ER.

Gallic acid attenuates blood-spinal cord barrier disruption by inhibiting Jmjd3 expression and activation after spinal cord injury.

After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.

Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation.

Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17ß-estradiol (100, 300 µg/kg) were administered to rats with neuropathic pain after SCI through intravenous injection. As results, both mechanical allodynia and thermal hyperalgesia were significantly reduced by 17ß-estradiol compared to vehicle control. Both microglia and astrocyte activation in the lamina I and II of L4-5 dorsal horn was also inhibited by 17ß-estradiol. In addition, the levels of p-p38MAPK and p-ERK known to be activated in microglia and p-JNK known to be activated in astrocyte were significantly decreased by 17ß-estradiol. Furthermore, the mRNA expression of inflammatory mediators such as Il-1ß, Il-6, iNos, and Cox-2 was more attenuated in 17ß-estradiol-treated group than in vehicle-treated group. Particularly, we found that the analgesic effect by 17ß-estradiol was mediated via estrogen receptors, which are expressed in dorsal horn neurons. These results suggest that 17ß-estradiol may attenuate SCI-induced neuropathic pain by inhibiting microglia and astrocyte activation followed inflammation.

Increased expression of IL-33 in rosacea skin and UVB-irradiated and LL-37-treated HaCaT cells.

Rosacea is one of the most common dermatoses of adults. Although the detailed pathophysiology remains unknown, it is thought that rosacea is caused by a consistently aberrant, innate immune response, and that LL-37 plays an important role. However, involvement of the inflammatory cytokine IL-33 has not yet been studied. We explored the role played by IL-33 in the pathophysiology of rosacea. First, we immunohistochemically evaluated the expression of IL-33 and its receptor (ST2) in rosacea skin. Second, we exposed HaCaT cells to ultraviolet B (UVB) irradiation in the presence or absence of LL-37 and measured the expression of proinflammatory cytokines including IL-33. We also analysed VEGF (vascular endothelial growth factor) mRNA expression and protein release after costimulation of HaCaT cells by LL-37 and IL-33. Immunohistochemically, IL-33 expression was enhanced in the skin of rosacea patients, especially with erythematotelangiectatic subtype. In vitro, UVB and LL-37 synergistically increased mRNAs expression of proinflammatory cytokines, especially IL-33 and IL-1ß. IL-33 protein release was also synergistically increased by LL-37 and UVB treatment. LL-37 and IL-33 stimulated VEGF mRNA expression and VEGF release from HaCaT cells. Our findings suggest that rosacea skin with abundant LL-37 may robustly produce and release IL-33 when exposed to UV radiation. IL-33 may participate in the angiogenesis and vasodilation of rosacea skin by enhancing VEGF release.

Matrix metalloproteinase-3 promotes early blood-spinal cord barrier disruption and hemorrhage and impairs long-term neurological recovery after spinal cord injury.

After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption by matrix metalloproteinases (MMPs) leads to BSCB permeability and blood cell infiltration, contributing to permanent neurological disability. Herein, we report that MMP-3 plays a critical role in BSCB disruption after SCI in mice. MMP-3 was induced in infiltrated neutrophils and blood vessels after SCI, and NF-κB as a transcription factor was involved in MMP-3 expression. BSCB permeability and blood cell infiltration after injury were more reduced in Mmp3 knockout (KO) mice than in wild-type (WT) mice, which was significantly inhibited by Mmp3 siRNA or a general inhibitor of MMPs, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid. The level of tight junction proteins, such as occludin and zonula occludens-1, which decreased after SCI, was also higher in Mmp3 KO than in WT mice. Exogenously, MMP-3 injection into the normal spinal cord also induced BSCB permeability. Furthermore, MMP-9 activation after injury was mediated by MMP-3 activation. Finally, improved functional recovery was observed in Mmp3 KO mice compared with WT mice after injury. These results demonstrated the role of MMP-3 in BSCB disruption after SCI for the first time and suggest that the regulation of MMP-3 can be considered a therapeutic target to inhibit BSCB disruption and hemorrhage, and thereby enhance functional recovery after acute SCI.

Nickel and cobalt release from jewellery and metal clothing items in Korea.

BACKGROUND: In Korea, the prevalence of nickel allergy has shown a sharply increasing trend. Cobalt contact allergy is often associated with concomitant reactions to nickel, and is more common in Korea than in western countries. OBJECTIVE: The aim of the present study was to investigate the prevalence of items that release nickel and cobalt on the Korean market. MATERIALS AND METHODS: A total of 471 items that included 193 branded jewellery, 202 non-branded jewellery and 76 metal clothing items were sampled and studied with a dimethylglyoxime (DMG) test and a cobalt spot test to detect nickel and cobalt release, respectively. RESULTS: Nickel release was detected in 47.8% of the tested items. The positive rates in the DMG test were 12.4% for the branded jewellery, 70.8% for the non-branded jewellery, and 76.3% for the metal clothing items. Cobalt release was found in 6.2% of items. Among the types of jewellery, belts and hair pins showed higher positive rates in both the DMG test and the cobalt spot test. CONCLUSION: Our study shows that the prevalence of items that release nickel or cobalt among jewellery and metal clothing items is high in Korea.

Factors associated with positive consequences of serving as a family caregiver for a terminal cancer patient.

BACKGROUND: We examined factors associated with positive consequences for family members who served as caregivers of terminal cancer patients. METHODS: We conducted a nationwide cross-sectional survey of 501 bereaved family members who served as caregivers for terminal cancer patients. The main outcomes were measured by the previously developed Caregiving Consequences Inventory, which assesses perceived rewards and burdens of caregiving. RESULTS: Bereaved family caregivers reported high levels of perceived rewards and burden. Among the characteristics of bereaved family members, older age, female gender, and having a religion were associated with some domains of perceived rewards, but being a spouse of a patient was negatively associated with some domains of perceived rewards. Caregiver depression or perceived burden did not affect positive consequences of caregiving. However, receiving bereavement care was significantly associated with positive outcome in all four perceived reward domains (sense of mastery [adjusted odds ratio {aOR} = 1.69; 95% CI, 1.05-2.70]; appreciation for others [aOR = 2.19; 95% CI, 1.27-3.76]; meaning in life [aOR = 1.80; 95% CI, 1.13-2.89]; and reprioritization about his/her life [aOR = 2.02; 95% CI, 1.27-3.19]). CONCLUSIONS: Family caregivers of terminal cancer patients experience burdens, but caregiving also has positive consequences. This study has important implications for the development of bereavement interventions that aim to encourage positive outcomes and reduce negative outcomes for caregivers.

Extended self-ordering regime in hard anodization and its application to make asymmetric AAO membranes for large pitch-distance nanostructures.

We report here a fast and reliable hard anodization process to make asymmetric anodic aluminum oxide (AAO) membranes which can serve as a template for large pitch-distance nanostructures. In order to make larger pitch distances possible, the common burning failure associated with the high current density during the conventional constant voltage hard anodization, especially at a voltage higher than a known limit, i.e., 155 V for oxalic acid, was effectively suppressed by using a burning-protective agent. A new self-ordering regime beyond the voltage limit was observed with a different voltage-interpore distance relationship of 2.2 nm V(-1) compared to the reported 2.0 nm V(-1) for hard anodization. Combining a sulfuric acid mild anodization with this new regime of hard anodization, we further demonstrate a scalable process to make an asymmetric membrane with size up to ~47 mm in diameter and ~60 µm in thickness. This free-standing membrane can be used as a template for novel nanopatterned structures such as arrays of quantum dots, nanowires or nanotubes with diameters of a few tens of nanometers and pitch distance of over 400 nm.

The complete mitochondrial genome of sleek unicornfish, Naso hexacanthus (Acanthuridae, Perciformes).

The complete mitochondrial DNA sequence of sleek unicornfish, Naso hexacanthus was first determined in this study. The complete mitogenome is 16,611 bp in length composed of 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. The nucleotides consist of 33.8% A, 20.6% C, 25.0% G, 20.6% T. The gene order and direction are identical to those of N. lopezi and the species of Acanthuridae. The result would be useful to investigate genetic relationships among the species of Naso.

Analysis of Positive Patch Test Allergens in Allergic Contact Dermatitis Patients with Atopic Dermatitis.

BACKGROUND: There has been debate regarding whether patients with atopic dermatitis (AD) have an altered frequency of contact allergen sensitization. Increased exposure to topical medications and moisturizers as well as impaired skin barrier function increase the risk of contact sensitization, whereas the Th2-skewed inflammatory pathway of AD is associated with a reduced risk. OBJECTIVE: This retrospective study was performed to determine the characteristics of contact sensitization in allergic contact dermatitis (ACD) patients with a current or past history of AD. METHODS: A clinical record review was conducted for patients referred to Ewha Womans University Medical Center, for patch tests between March 2017 and March 2021. We compared the rates of contact sensitization between ACD patients with and without AD. RESULTS: In total, 515 patch test results were reviewed and divided into the AD group (n=53) and non-AD group (n=462). The AD group showed decreased any-allergen positivity (1+, 2+, or 3+) (56.6%) compared to the non-AD group (72.9%) (p=0.013). The positivity rate for budesonide was significantly higher in the AD group (p=0.011), while the prevalence of a positive result for balsam of Peru was higher in the non-AD group (p=0.036). Nickel sulfate, cobalt chloride, and potassium dichromate were the most common sensitized allergens in both groups. CONCLUSION: Our study shows a decreased prevalence of contact sensitization in AD patients compared to non-AD patients. Clinicians should be aware of the risk of corticosteroid allergies in ACD patients with history of AD.

Free-standing TiO2 nanograssy tubular hybrid membrane for polysulfide trapping in Li-S battery.

During the growth of anodic TiO2 nanotubes with a high layer thickness of greater than 20 µm, "nanograss" structures are typically formed on the outermost surface. This happens due to the fact that the engraving of the oxide tubes arises during prolonged exposure to an F- ion containing electrolyte. These TiO2 nanotubular layers have a high aspect ratio with astonishing bundles of nanograss structures on the tube top and especially a high surface area with anatase crystallites in the tubes. By two-step anodization in synergy with the hybridization of a rubber polymer binder, freestanding nanotubular layers consisting of nanograssy surfaces with nano-crystalline particles in the tubes were successfully obtained. Under the highly efficient polysulfide trapping and electrolyte perturbation, this nanotubular hybrid membrane could deliver an enriched performance with a capacity of 618 mA h g-1 after 100 cycles at 0.1C in Li-S batteries.

A Case of Linear Hypertrophic Lichen Planus in a Pediatric Patient.

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucosa. Of the various types, the hypertrophic type is characterized by thickened, purplish hyperkeratotic plaques and nodules. The course of hypertrophic LP tends to be more chronic than those of other types. A 12-year-old girl presented with a 2-year history of warty papules and plaques in a zosteriform configuration along one flank. Histopathology revealed hyperkeratosis and papillomatosis with wedge-shaped hypergranulosis. A lichenoid lymphocytic infiltrate with vacuolar change in the basal layer was evident. She was prescribed oral doxycycline, a topical corticosteroid, and tacrolimus. After 7 weeks, the skin lesions became significantly flattened and faded. LP is less common but more severe in children than in adults. The unilateral, linear hypertrophic type of LP is uncommon. Herein, we report a rare case of linear hypertrophic LP in a child.

Interferometric fiber optic sensors.

Fiber optic interferometers to sense various physical parameters including temperature, strain, pressure, and refractive index have been widely investigated. They can be categorized into four types: Fabry-Perot, Mach-Zehnder, Michelson, and Sagnac. In this paper, each type of interferometric sensor is reviewed in terms of operating principles, fabrication methods, and application fields. Some specific examples of recently reported interferometeric sensor technologies are presented in detail to show their large potential in practical applications. Some of the simple to fabricate but exceedingly effective Fabry-Perot interferometers, implemented in both extrinsic and intrinsic structures, are discussed. Also, a wide variety of Mach-Zehnder and Michelson interferometric sensors based on photonic crystal fibers are introduced along with their remarkable sensing performances. Finally, the simultaneous multi-parameter sensing capability of a pair of long period fiber grating (LPG) is presented in two types of structures; one is the Mach-Zehnder interferometer formed in a double cladding fiber and the other is the highly sensitive Sagnac interferometer cascaded with an LPG pair.

Precise temperature mapping of GaN-based LEDs by quantitative infrared micro-thermography.

A method of measuring the precise temperature distribution of GaN-based light-emitting diodes (LEDs) by quantitative infrared micro-thermography is reported. To reduce the calibration error, the same measuring conditions were used for both calibration and thermal imaging; calibration was conducted on a highly emissive black-painted area on a dummy sapphire wafer loaded near the LED wafer on a thermoelectric cooler mount. We used infrared thermal radiation images of the black-painted area on the dummy wafer and an unbiased LED wafer at two different temperatures to determine the factors that degrade the accuracy of temperature measurement, i.e., the non-uniform response of the instrument, superimposed offset radiation, reflected radiation, and emissivity map of the LED surface. By correcting these factors from the measured infrared thermal radiation images of biased LEDs, we determined a precise absolute temperature image. Consequently, we could observe from where the local self-heat emerges and how it distributes on the emitting area of the LEDs. The experimental results demonstrated that highly localized self-heating and a remarkable temperature gradient, which are detrimental to LED performance and reliability, arise near the p-contact edge of the LED surface at high injection levels owing to the current crowding effect.

Prognostic factors in diabetes: Comparison of Chi-square automatic interaction detector (CHAID) decision tree technology and logistic regression.

This study aimed to develop a diabetes prediction model. The model performance was compared with logistic regression, and the decision tree Chi-square automatic interaction detection (CHAID) was used to predict diabetes. In total, 3233 patients were included in the analysis. Of these, 589 patients with diabetes and 2644 patients without diabetes were included after analyzing the study sample from the Korean Genome and Epidemiology Study (KoGES)-8 data. In this study, Diabetes Mellitus (DM) diagnosis prediction was compared with logistic regression and prediction through machine learning (ML) using the CHAID decision classification tree. We performed statistical analysis using the CHAID method with International Business Machine (IBM) statistical program SPSS®. We performed logistic regression analysis to predict the classification of diabetes accurately, and the total classification accuracy of the analysis was 81.7%, and the CHAID decision tree classification accuracy was 81.8%. A diabetes diagnosis decision tree was created, which included seven terminal nodes and three depth levels. This analysis showed that a blood pressure problem and hospital visits were the most decisive variables at the time of classification, and two risk levels were created for diabetes diagnosis. The suggested method is a valuable tool for predicting diabetes. Patients who visit the hospital because of blood pressure problems are more likely to develop diabetes than under-treating hyperlipidemia. The diabetes prediction model can help doctors make decisions by detecting the possibility of diabetes early; however, it is impossible to diagnose diabetes using only the model without the doctor's opinion.

Suppression of Transient Receptor Potential Melastatin 7 by Carvacrol Protects against Injured Spinal Cord by Inhibiting Blood-Spinal Cord Barrier Disruption.

When the blood-spinal cord barrier (BSCB) is disrupted after a spinal cord injury (SCI), several pathophysiological cascades occur, including inflammation and apoptotic cell death of neurons and oligodendrocytes, resulting in permanent neurological deficits. Transient receptor potential melastatin 7 (TRPM7) is involved in the pathological processes in many neuronal diseases, including traumatic brain injury, amyotrophic lateral sclerosis, parkinsonism dementia, and Alzheimer's disease. Further, carvacrol (CAR), a TRPM7 inhibitor, is known to protect against SCI by reducing oxidative stress and inhibiting the endothelial nitric oxide synthase pathway. However, the functions of TRPM7 in the regulation of BSCB homeostasis after SCI have not been examined. Here, we demonstrated that TRPM7, a calcium-mediated non-selective divalent cation channel, plays a critical role after SCI in rats. Rats were contused at T9 and given CAR (50 mg/kg) intraperitoneally immediately and 12 h after SCI, and then given the same dose once a day for 7 days. TRPM7 was found to be up-regulated after SCI in both in vitro and in vivo studies, and it was expressed in blood vessels alongside neurons and oligodendrocytes. Additionally, CAR treatment suppressed BSCB disruption by inhibiting the loss of tight junction (TJ) proteins and preserved TJ integrity. CAR also reduced apoptotic cell death and improved functional recovery after SCI by preventing BSCB disruption caused by blood infiltration and inflammatory responses. Based on these findings, we propose that blocking the TRPM7 channel can inhibit the destruction of the BSCB and it is a potential target in therapeutic drug development for use in SCI.

A Case of Vesicular Mycosis Fungoides.

A 44-year-old male presented with 7 months history of nonpruritic round oozing plaques on the extremities and red papules on the trunk. The lesions were resistant to topical and oral steroid prescribed at the other local clinics. Histopathological examination showed parakeratosis with acanthosis and rete ridge elongation as well as spongiotic intraepidermal blisters and dense dermal infiltration of small to medium sized atypical lymphoid cells. Immunohistochemical analysis revealed the lymphocyte infiltrate to be predominantly CD4+ T cells, with CD4/CD8 ratio to be greater than 10:1. Infiltration of large cells that were CD30+ were also noted. This histopathologic findings are consistent with vesicular mycosis fungoides (MF). He was prescribed with narrow-band ultraviolet B twice per week and topical steroid, combined with interferon-α injection for 5 weeks, and his skin lesions significantly faded and were flattened. Vesicular MF is associated with poor prognosis, but our patient was able to show benign course of disease thanks to timely diagnosis. One must consider vesicular MF as a differential for recalcitrant eczematous lesions.

Microlensed dual-fiber probe for depth-resolved fluorescence measurements.

We propose and demonstrate a compact microlensed dual-fiber probe that has a good collection efficiency and a high depth-resolution ability for fluorescence measurements. The probe is formed with a conventional fusion splicer creating a common focusing lens on two fibers placed side by side. The collection efficiency of the fabricated probe was evaluated by measuring the fluorescence signal of a fresh ginkgo leaf. It was shown experimentally that the proposed probe could effectively collect the fluorescence signal with a six-fold increase compared to that of a general flat-tipped probe. The beam propagation method was used to design a probe with an optimized working distance and an improved resolving depth. It was found that the working distance depends mainly on the radius of curvature of the lens, whereas the resolving depth is determined by the core diameters of the illumination and collection fibers. The depth-resolved ability of probes with working distances of ~100 µm and 300 µm was validated by using a two-layer tissue phantom. The experimental results demonstrate that the microlensed dual-fiber probe has the potential to facilitate depth-resolved fluorescence detection of epithelial tissue.