Sleep Disturbances in Children With Atopic Dermatitis: A Scoping Review.

Atopic dermatitis (AD) is associated with various quality of life concerns including poor sleep. Sleep impairments in children with AD are associated with increased risk of short stature, metabolic syndrome, mental illness and neurocognitive dysfunction. Although the association between AD and sleep disturbance is well established, the specific types of sleep disturbance in pediatric AD patients and their underlying mechanisms are not fully understood. A scoping literature review was performed to characterize and summarize the types of sleep disturbance in children (less than 18 years of age) with AD. 31 papers met inclusion criteria and extracted data were analyzed in an iterative manner. Two types of sleep disturbances were found to be more prevalent in pediatric AD patients in comparison to controls. One category was related to loss of sleep (increased frequency or duration of awakenings, increased sleep fragmentation, delayed sleep onset, decreased total sleep duration, and decreased sleep efficiency). Another category was associated with unusual behaviors during sleep (restlessness/limb movement/scratching, sleep-disordered breathing including obstructive sleep apnea and snoring, nightmares, nocturnal enuresis and nocturnal hyperhidrosis). Some mechanisms underlying these sleep disturbances include pruritus and induced scratching and increased proinflammatory markers induced by sleep loss. Sleep disturbance appears to be associated with AD. We recommend clinicians to consider interventions that may reduce sleep disturbances in children with AD. Further investigation of these sleep disturbances is needed to elucidate pathophysiology, develop additional treatments, and reduce negative impacts on the health outcomes and quality of life in pediatric AD patients.

Perspectives and knowledge of acne vulgaris among young adolescents.

Acne occurs in up to 90% of young adolescents, but prior research has found that this population exhibits a limited understanding of acne and is vulnerable to myths and misinformation accumulated from family members, friends, and social media. We created a virtual presentation on skin hygiene, acne prevention, and acne-associated stigma for adolescent youth (aged 9-13) to improve acne health literacy, which was reviewed by three board-certified dermatologists. A descriptive cross-sectional study using data collected for quality improvement (n = 209, total) revealed that approximately half (n = 102/202, 50.5%) of all students believed that acne could not be treated with medications, only 34.0% (n = 67/197) believed acne could impact their mental health, and most students incorrectly believed that dirt buildup (n = 124/209, 59.3%) and poor hygiene (n = 125/209, 59.8%) were pathogenic for acne. Our results stress the necessity of early evidence-based educational interventions as a cornerstone to breaking self-perpetuating myths and misinformation that may lead to acne mismanagement, delayed access to healthcare, and permanent scarring later in life.

Data-Driven Prediction of Fatigue in Parkinson's Disease Patients.

Introduction: Numerous non-motor symptoms are associated with Parkinson's disease (PD) including fatigue. The challenge in the clinic is to detect relevant non-motor symptoms while keeping patient-burden of questionnaires low and to take potential subgroups such as sex differences into account. The Fatigue Severity Scale (FSS) effectively detects clinically significant fatigue in PD patients. Machine learning techniques can determine which FSS items best predict clinically significant fatigue yet the choice of technique is crucial as it determines the stability of results. Methods: 182 records of PD patients were analyzed with two machine learning algorithms: random forest (RF) and Boruta. RF and Boruta calculated feature importance scores, which measured how much impact an FSS item had in predicting clinically significant fatigue. Items with the highest feature importance scores were the best predictors. Principal components analysis (PCA) grouped highly related FSS items together. Results: RF, Boruta and PCA demonstrated that items 8 ("Fatigue is among my three most disabling symptoms") and 9 ("Fatigue interferes with my work, family or social life") were the most important predictors. Item 5 ("Fatigue causes frequent problems for me") was an important predictor for females, and item 6 ("My fatigue prevents sustained physical functioning") was important for males. Feature importance scores' standard deviations were large for RF (14-66%) but small for Boruta (0-5%). Conclusion: The clinically most informative questions may be how disabling fatigue is compared to other symptoms and interference with work, family and friends. There may be some sex-related differences with frequency of fatigue-related complaints in females and endurance-related complaints in males yielding significant information. Boruta but not RF yielded stable results and might be a better tool to determine the most relevant components of abbreviated questionnaires. Further research in this area would be beneficial in order to replicate these findings with other machine learning algorithms, and using a more representative sample of PD patients.

Association of 10-Year Atherosclerotic Cardiovascular Disease Risk Score with Carotid Intima-Media Thickness and Plaque.

BACKGROUND: The aim of this study was to determine the association between carotid intima-media thickness (IMT) and newly developed 10-year atherosclerotic cardiovascular disease (ASCVD) risk score. METHODS: Participants were 201 Korean adults who underwent carotid ultrasonography at the Health Promotion Center of the Eulji General Hospital. We obtained information about medical history and lifestyle, and conducted laboratory tests. Carotid IMT by B-mode ultrasonography was measured. Carotid injury was considered present when the maximum carotid IMT was ≥0.9 mm or when arteriosclerotic plaques were detected. The 10-year ASCVD risk score was calculated using the 2013 American College of Cardiology/American Heart Association guidelines. RESULTS: Men had higher 10-year ASCVD risk score than did women (mean±standard deviation: 7.15±6.04 vs. 2.53±3.67, respectively; P<0.001). Ten-year ASCVD risk was significantly correlated with right maximum carotid IMT (r=0.307), left maximum carotid IMT (r=0.230), right mean carotid IMT (r=0.322), and left mean carotid IMT (r=0.264). The group with high 10-year ASCVD risk were at even higher risk of carotid injury than were the group with low 10-year ASCVD risk (odds ratio, 2.201; 95% confidence interval, 1.162-4.1706; P=0.019). Only 10-year ASCVD risk score was significantly associated with carotid injury (odds ratio, 4.104; 95% confidence interval, 1.570-10.729). Variables that were not included in the 10-year ASCVD risk score were not significantly associated with carotid injury. CONCLUSION: The findings of this study suggest that 10-year ASCVD risk score is associated with carotid injury.

N-3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice.

BACKGROUND AND AIM: The increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve gallstones. In investigating novel therapeutics for CG, we assessed the preventive effects of n-3 polyunsaturated fatty acids (n-3PUFA) on the formation of CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice. METHODS: Mice were divided into the following six groups: (A) regular diet (RD); (B) RD+n-3PUFA; (C) LD; (D) LD+n-3PUFA; (E) LD+UDCA; (F) LD+n-3PUFA+UDCA. After RD/LD feeding for 2 weeks, n-3PUFA or UDCA was administered orally and the diet maintained for 8 weeks. The levels of phospholipids and cholesterol in bile, CG formation, gallbladder wall thickness, MUC gene expression in gallbladder were analyzed. RESULTS: No stone or sludge was evident in the RD groups (Groups A, B). Mice in the n-3PUFA treatment (Groups D, F) showed significantly lower stone formation than the other LD groups (Groups C, E). The combination treatment of n-3PUFA and UDCA suppressed stone formation more than mono-therapy with n-3PUFA or UDCA. Bile phospholipid levels were significantly elevated in the Group F. Hypertrophy of the gallbladder wall was evident in mice fed LD. MUC 2, 5AC, 5B and 6 mRNA expression levels were significantly elevated in the LD-fed group, and this was suppressed by n-3PUFA with or without UDCA. CONCLUSIONS: N-3PUFA attenuated gallstone formation in mouse, through increasing the levels of bile phospholipids and suppressing bile mucin formation.

Functional expression and characterization in Xenopus laevis oocytes of the ABCG2 transporter derived from A549 human lung adenocarcinoma cells.

We cloned the ATP-binding cassette sub-family G member 2 (ABCG2) transporter, the most recently identified among several major human multidrug-resistance pumps, from A549 human lung adenocarcinoma cells in order to characterize its function and substrate specificity. In a previous report, we confirmed that a stem cell-like side population of A549 cells highly expressed the ABCG2 gene and had a unique ability to resist the anticancer drug methotrexate (MTX). In this study, ABCG2 cDNA was cloned by RT-PCR and converted into cRNA by an in vitro transcription system for expression in Xenopus laevis (X. laevis) oocytes. The transcribed cRNA of the ABCG2 gene was injected into the oocytes under the absence of cofactors or heterologous partner proteins or some lipids from the media. A high expression of ABCG2 was observed on the oocyte surface by immunofluorescence and confocal laser microscopy. We tested the functional effect of ABCG2 expression on drug efflux by directly injecting MTX into X. laevis oocytes. The drug concentration within the oocytes was quantified with LC-MS/MS; the analysis showed that the accumulation of MTX was significantly decreased in the X. laevis oocytes expressing ABCG2 compared with the control oocytes not expressing ABCG2. These findings show that the ABCG2 protein has an important role in the efflux of MTX through the cell membrane of X. laevis oocytes. Therefore, it might be that ABCG2, abundantly expressed in the stem cell population of A549 cells, can modulate resistance to MTX in lung cancer therapy.

Nonlinear toxicokinetics of enrofloxacin in rats.

The dose-dependent toxicokinetics of enrofloxacin were studied by administering various single subcutaneous doses (5, 10, 20, 40, 70, 100, 150, 200, 300 and 400 mg/kg) in male Sprague-Dawley rats. The blood samples were collected from the tail veins, and the plasma concentration of enrofloxacin was determined by an HPLC-fluorescence detection (FLD) method. The time-concentration profiles of enrofloxacin were well fitted by an one-compartmental model with first order elimination. The absorption half-lives (t1(/)2(abs)) ranged from 0.2-0.8 h, and the mean time to maximum plasma concentration (T(max)) ranged from 0.6-1.8 h. On the other hand, marked disproportionate increases of the area under the curve (AUC) and elimination half-lives (t1(/)2) were observed from the increase of the doses. This result indicates that the elimination of enrofloxacin has nonlinear pharmacokinetic properties with increasing doses. Therefore, we need to take into consideration the possible occurrence of side effects resulting from greater systemic exposure from high dose therapies.

Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel.

BACKGROUND: We have studied the in vitro and in vivo utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system. METHODS: A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 x 10(6). Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study. RESULTS: In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group. CONCLUSION: We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.

Single-step extraction followed by LC for determination of (fluoro)quinolone drug residues in muscle, eggs, and milk.

In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary.

Comparative gene expression of intestinal metabolizing enzymes.

The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3, CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3 and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly expressed in the mouse. The rat revealed predominant expression of glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1, acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human, glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3, GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore, current data indicated substantial interspecies differences in the pattern of intestinal gene expression both for P450 enzymes and phase II drug-metabolizing enzymes. This genomic database is expected to improve our understanding of interspecies variations in estimating intestinal prehepatic clearance of oral drugs.