Dichotomous versus 5-scale grading system for the interpretation of the point-of-care immunoassay for tear matrix metalloproteinase-9 in dry eye.

In this study, we compared the dichotomous and 5-scale grading systems for point-of-care immunoassay of tear matrix metalloproteinase (MMP)-9 in dry eye disease (DED) patients and identified the optimal dichotomous system to correlate with DED parameters. We included 167 DED patients without primary Sjogren's syndrome (pSS) (Non-SS DED) and 70 DED patients with pSS (SS DED). We graded MMP-9 expression in InflammaDry® (Quidel, San Diego, CA, USA) using a 5-scale grading system and dichotomous grading systems with four different cut-off grades (D1 to D4 systems). The only DED parameter that showed a significant correlation with the 5-scale grading method was tear osmolarity (Tosm). In both groups, subjects with positive MMP-9 had lower tear secretion and higher Tosm than those with negative MMP-9 according to the D2 dichotomous system. Tosm determined D2 positivity at cutoffs > 340.5 and > 317.5 mOsm/L in the Non-SS DED and SS DED groups, respectively. Tear secretion < 10.5 mm or tear break-up time < 5.5 s stratified D2 positivity in the Non-SS DED group. In conclusion, the dichotomous grading system of InflammaDry reflects ocular surface indices better than the 5-scale grading system and may be more practical in real clinical circumstances.

Neural network-based method for diagnosis and severity assessment of Graves' orbitopathy using orbital computed tomography.

Computed tomography (CT) has been widely used to diagnose Graves' orbitopathy, and the utility is gradually increasing. To develop a neural network (NN)-based method for diagnosis and severity assessment of Graves' orbitopathy (GO) using orbital CT, a specific type of NN optimized for diagnosing GO was developed and trained using 288 orbital CT scans obtained from patients with mild and moderate-to-severe GO and normal controls. The developed NN was compared with three conventional NNs [GoogleNet Inception v1 (GoogLeNet), 50-layer Deep Residual Learning (ResNet-50), and 16-layer Very Deep Convolutional Network from Visual Geometry group (VGG-16)]. The diagnostic performance was also compared with that of three oculoplastic specialists. The developed NN had an area under receiver operating curve (AUC) of 0.979 for diagnosing patients with moderate-to-severe GO. Receiver operating curve (ROC) analysis yielded AUCs of 0.827 for GoogLeNet, 0.611 for ResNet-50, 0.540 for VGG-16, and 0.975 for the oculoplastic specialists for diagnosing moderate-to-severe GO. For the diagnosis of mild GO, the developed NN yielded an AUC of 0.895, which is better than the performances of the other NNs and oculoplastic specialists. This study may contribute to NN-based interpretation of orbital CTs for diagnosing various orbital diseases.

Assessment of reliability and validity of the 5-scale grading system of the point-of-care immunoassay for tear matrix metalloproteinase-9.

We evaluated the reliability and validity of the 5-scale grading system to interpret the point-of-care immunoassay for tear matrix metalloproteinase (MMP)-9. Six observers graded red bands of photographs of the readout window in MMP-9 immunoassay kit (InflammaDry) two times with 2-week interval based on the 5-scale grading system (i.e. grade 0-4). Interobserver and intraobserver reliability were evaluated using intraclass correlation coefficients. The interobserver agreements were analyzed according to the severity of tear MMP-9 expression. To validate the system, a concentration calibration curve was made using MMP-9 solutions with reference concentrations, then the distribution of MMP-9 concentrations was analyzed according to the 5-scale grading system. Both intraobserver and interobserver reliability was excellent. The readout grades were significantly correlated with the quantified colorimetric densities. The interobserver variance of readout grades had no correlation with the severity of the measured densities. The band density continued to increase up to a maximal concentration (i.e. 5000 ng/mL) according to the calibration curve. The difference of grades reflected the change of MMP-9 concentrations sensitively, especially between grade 2 and 4. Together, our data indicate that the subjective 5-scale grading system in the point-of-care MMP-9 immunoassay is an easy and reliable method with acceptable accuracy.

Effectiveness of self-re-learning using video recordings of advanced life support on nursing students' knowledge, self-efficacy, and skills performance.

BACKGROUND: Nurses are presumably the first to see an in-hospital cardiac arrest patient. This study proposed measuring nursing students' knowledge, self-efficacy, and skills performance in advanced life support (ALS), 6 months after training, by sending videos taken during their final skills test after the ALS training. METHODS: This is an experimental study using a randomised control group design. This study was conducted from June to December 2018, and the subjects of the study were 4th year students, recruited through a bulletin board at a nursing university. The participants' knowledge, self-efficacy, and skill performance in ALS were evaluated immediately after the training, and participants were videotaped during the final skills test. Thereafter, the videos were sent to the experimental group through a mobile phone messenger application, once a month, from the third month after training. Approximately six months after training day, a follow-up test was conducted for the measured variables using a blinded method. The paired t-test and Wilcoxon signed-rank test were used to compare the two groups pre-and post-intervention. The statistical significance level was set at p < .05. RESULTS: Six months after the ALS training, knowledge scores decreased significantly in both groups (p < 0.001). Self-efficacy decreased by about 3 points from 50.55 to 47.18 in the experimental group (p = 0.089), while it decreased by 10 points in the control group, from 50.67 to 39 (p < 0.001). The skills performance decreased from 27.5 to 26.68 in the experimental group, while it decreased significantly from 27.95 to 16.9 in the control group (p < 0.001). CONCLUSION: Self-study with videos taken during an ALS skills test helps enhance the sustainable effects of training such as knowledge, self-efficacy, and skills performance.

Changes in Muscle Mass after Botulinum Toxin Injection in Children with Spastic Hemiplegic Cerebral Palsy.

We aimed to evaluate muscle mass changes after injection of botulinum toxin (BoNT) in children with spastic hemiplegic cerebral palsy (CP). Children aged between 2 and 12 years who were diagnosed with hemiplegic CP with spastic equinus foot were prospectively recruited and administered BoNT in the affected leg. Lean body mass (LBM) of both legs and total limbs was measured by dual-energy X-ray absorptiometry (DXA) preinjection and 4 and 12 weeks after injection. A total of 15 children were enrolled into the study. LBM of both legs and total limbs increased significantly over 12 weeks of growth. The ratio of LBM of the affected leg to total limbs and to the unaffected leg significantly reduced at 4 weeks after injection compared with preinjection but significantly increased at 12 weeks after injection compared with 4 weeks after injection. In conclusion, the muscle mass of the affected leg after BoNT injection in children with hemiplegic spastic CP decreased at 4 weeks after BoNT injection but significantly recovered after 12 weeks after injection.

Correlations between choroidal thickness and renal function in patients with retinal vein occlusion.

The purpose of this study was to analyze the correlation of renal function indices with sub-foveal choroidal thickness (SFChT) in treatment-naïve (naïve) eyes with retinal vein occlusion (RVO) using swept-source optical coherence tomography (SS-OCT) and systemic workup. Retrospective chart review was performed from Dec 2016 to Sep 2019 in patients newly diagnosed with treatment-naïve unilateral RVO. Ocular parameters, including SFChT, and systemic profiles, including renal function indices, were reviewed. Simple and multiple linear regression analyses were performed to check if there was a correlation between renal profiles and SFChT. A total of 56 patients were included in the study; 34 of them were branch RVO and 22 were central RVO patients. Multiple linear regression analysis revealed that SFChT was positively correlated with estimated glomerular filtration rate (eGFR) (P < 0.001). SFChT showed significant correlation with renal function indices. In addition, choroidal thickness may be considered as systemic biomarkers for renal function.

Korean language specific dysarthria associated with idiopathic peripheral facial palsy.

To investigate the patterns of dysarthria in Korean patients with idiopathic peripheral facial palsy.Seventy-eight patients diagnosed with idiopathic peripheral facial palsy within the onset of symptom to 7 day time frame were prospectively enrolled. The initial symptom of facial palsy was examined by the House-Brackmann scale. All patients were tested by Urimal-Test of Articulation and Phonology-2 (U-TAP-2), which is specialized for the evaluation of dysarthria in Korean language - Hangeul - when the patients first visited and were followed up at 4 weeks after the onset, respectively. The facial electromyography was performed after 7 days, since the presentation of the first symptom. Electric stimulation therapy and simple facial exercise education were performed in all patients as routine treatments for facial palsy with or without dysarthria. The patterns of dysarthria were analyzed by initial and follow-up U-TAP-2 results, respectively.Among 78 patients, 50 patients (64.1%) had dysarthria in the first assessment. The 6 consonants and 3 vowels were errored in U-TAP-2 test. The bilabial consonants "ㅃ"[p] or "ㅍ" [p] were substituted with labiodental consonant [f], and palate-alveolar consonants were replaced by alveolar consonants - "ㅊ"[t(Equation is included in full-text article.)] to "ㅌ"[t]. Bilabial consonant "ㅁ"[m] was replaced by velar nasal consonant "ㅇ"[ŋ]. Liquid consonant was altered to nasal sound. For example, "ㄹ"[r] is replace by "ㄴ"[n]. The velar consonant "ㄲ"[k] was pronounced as "ㅋ" [k]. The diphthong vowels "ㅟ"[[Latin Small Letter Turned H]i], "ㅚ"[ø], or "ㅘ"[wa] were pronounced as monothong "ㅣ" [i], "ㅐ"[ε], or "ㅏ"[a], and "못"[mot] is slowly pronounced. After 4 weeks, 14 patients still showed pronunciation errors in 5 consonants and 3 vowels. The most common error was substitution.Among 78 patients with idiopathic peripheral facial palsy, 50 patients had dysarthria and 14 out of 50 patients with dysarthria lasted more than 4 weeks. Five consonants ("ㅁ", "ㅊ", "ㅍ", "ㄹ", "ㄲ") and 3 vowels ("ㅘ", "ㅗ", "ㅟ or ㅚ") were still mispronounced after 4 weeks, and most common error was substitution. Therefore, speech evaluation and speech therapy specialized for errors in high frequency of consonants and vowels are needed in patients with idiopathic peripheral facial palsy, in Korea.

Changes in Lower Eyelid Position and Shape After Inferior Orbital Wall Reconstruction.

PURPOSE: To use morphological measurements to analyze changes in the position and shape of the lower eyelid after inferior orbital wall reconstruction. METHODS: This study included 47 eyes from 47 patients with blowout fractures. Digital photographs were taken in primary gaze immediately before and after surgery; the degree of enophthalmos was recorded. Several eyelid parameters were measured, including marginal reflex distance 1 (MRD1), MRD2, lower eyelid length (LEL), lower medial palpebral fissure area, lower central palpebral fissure area (LCA), and lower lateral palpebral fissure area. RESULTS: The exophthalmometry values (P < 0.001), MRD2 (P < 0.001), LEL (P < 0.001), LCA (P = 0.022), and lower lateral palpebral fissure area (P = 0.038) on the injured side before surgery were significantly smaller than those on the contralateral, uninjured side. Following surgery, the MRD2 increased from 5.01 ±â€Š0.65 mm to 5.60 ±â€Š0.78 mm (P < 0.001), LEL from 25.62 ±â€Š2.11 mm to 26.64 ±â€Š2.29 mm (P < 0.001), lower medial palpebral fissure area from 7.10 ±â€Š3.97 mm to 10.37 ±â€Š3.40 mm (P < 0.001), and LCA from 20.28 ±â€Š4.79 mm to 21.25 ±â€Š5.14 mm (P = 0.008). Multivariate linear regression analysis revealed that changes in the MRD2 (P = 0.019) and LCA (P = 0.048) were associated with enophthalmos improvement. CONCLUSION: The central and medial portions of the lower eyelid are retracted after inferior orbital reconstruction in patients with blowout fractures. The amount of central retraction on the lower eyelid is associated with the amount of enophthalmos improvement.

Botulinum Toxin Injection in Children with Hemiplegic Cerebral Palsy: Correction of Growth through Comparison of Treated and Unaffected Limbs.

Botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP) may negatively affect muscle growth and strength. We injected BoNT-A into the affected limbs of 14 children (4.57 ± 2.28 years) with hemiplegic CP and exhibiting tip-toeing gait on the affected side and investigated the morphological alterations in the medial head of the gastrocnemius muscle (GCM). We assessed thickness of the GCM, fascicle length, and fascicle angle on the affected and unaffected sides at baseline at 4 and 12 weeks after BoNT-A injections. The primary outcome measure was the change (percentage) in GCM thickness in the affected side treated with BoNT-A in comparison with the unaffected side. The percentage of treated GCM thickness became significantly thinner at 4 and 12 weeks after BoNT-A injection than baseline. However, the percentage of fascicle length and angle in treated limbs showed no significant change from baseline 4 and 12 weeks after the injection. BoNT-A injections might reduce muscle thickness in children with spastic hemiplegic CP. Fascicle length and angle might not be affected by BoNT-A injections after correction of normal growth of the children.

Patient With Delayed Development Resulting From De Novo Duplication of 7q36.1-q36.3 and Deletion of 9p24.3.

Patients with a duplication from 7q36 to the terminus or a deletion of 9p24 have been reported, whereas those harboring both mutations have not. Here, we report a patient with simultaneous de novo 7q36.1-q36.3 duplication and 9p24.3 deletion. A 6-year-old boy presented with speech developmental delay, microcephaly, and dysmorphic features, including a long face and small nose. Chromosome and array comparative genomic hybridization analyses revealed 46,XY,dup(7)(q36.1-q36.3) and del(9)(p24.3). The sizes of the duplication and deletion were 9.9 Mb and 1.9 Mb, respectively. The duplication of chromosome 7 contained 68 known genes, of which 3 are related with entries in the Developmental Disorders Genotype-to-Phenotype (DDG2P) database. The deletion of chromosome 9 contained 6 known genes, of which 2 are in the DDG2P database. We investigated the genotype and phenotype in this patient, and reviewed the relevant literatures for possible clinical presentation in these variations.

Protective effect of Salvia miltiorrhiza Bunge on 5-fluorouracil-induced oral mucositis.

Oral mucositis is a common side-effect caused by chemotherapy or radiotherapy occurring in the majority of cancer patients and is characterized by inflammation and ulcers in the oral mucosa. In the present study, we examined the protective effects of Salvia miltiorrhiza Bunge (SM) on oral mucositis induced by 5-fluorouracil (5-FU) in human pharyngeal cells and golden Syrian hamsters. We investigated the proliferation and antioxidant abilities of SM using MTT, 2-diphenyl-1-picrylhydrazyl (DPPH) and reactive oxygen species (ROS) assays in vitro. Additionally, TUNEL assay was performed, and the expression levels of nuclear factor-κB (NF-κB), caspase-3 and proinflammatory cytokines were assessed by immunoblotting. The results showed that SM increased the cell proliferation rate in human pharyngeal cells up to 128.97±9.7% compared with this rate in the untreated cells and exerted protective effects on mucosal injury caused by 5-FU treatment. In addition, all concentrations of SM increased DPPH scavenging ability and blocked ROS generation in the treated cells. Taken together, following SM treatment, expression of NF-κB and cleaved caspase-3 were significantly decreased followed by inhibition of cell death. These data suggest that SM could be used for the prevention and treatment of oral mucositis caused by cancer therapies.

A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia.

ETHNOPHARMACOLOGICAL RELEVANCE: Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly. METHODS: This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60-80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks. RESULTS: VAS for xerostomia was decreased by 22.04±22.76 in the YMJ group and 23.58±23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37kg/m(2) showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant. CONCLUSION: A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD.

Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report.

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11. One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.