Microneedles: A novel clinical technology for evaluating skin characteristics.

BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment. Non-invasive devices measured skin aging (using high-resolution 3D-imaging in the anti-aging study) or pigmentation (using spectrophotometry in the anti-pigmentation study) at weeks 0 and 4, and adverse skin reactions were monitored. Skin samples were collected with biocompatible microneedle patches. Changes in expression of biomarkers for skin aging and pigmentation were analyzed using qRT-PCR. RESULTS: No adverse events were reported. In the anti-aging study, after 4 weeks, skin roughness significantly improved in 17 out of 20 participants. qRT-PCR showed significantly increased expression of skin-aging related biomarkers: PINK1 in 16/20 participants, COL1A1 in 17/20 participants, and MSN in 16/20 participants. In the anti-pigmentation study, after 4 weeks, skin lightness significantly improved in 16/20 participants. qRT-PCR showed significantly increased expression of skin-pigmentation-related biomarkers: SOD1 in 15/20 participants and Vitamin D Receptor (VDR) in 15/20 participants. No significant change in TFAP2A was observed. CONCLUSION: Skin sampling and mRNA analysis for biomarkers provides a novel, objective, quantitative method for measuring changes in the dermis and evaluating the efficacy of cosmetics. This approach complements existing evaluation methods and has potential application in assessing the effectiveness of medical devices, medications, cosmeceuticals, healthy foods, and beauty devices.

Mitigating biomass composition uncertainties in flux balance analysis using ensemble representations.

The biomass equation is a critical component in genome-scale metabolic models (GEMs): it is used as the de facto objective function in flux balance analysis (FBA). This equation accounts for the quantities of all known biomass precursors that are required for cell growth based on the macromolecular and monomer compositions measured at certain conditions. However, it is often reported that the macromolecular composition of cells could change across different environmental conditions and thus the use of the same single biomass equation in FBA, under multiple conditions, is questionable. Herein, we first investigated the qualitative and quantitative variations of macromolecular compositions of three representative host organisms, Escherichia coli, Saccharomyces cerevisiae and Cricetulus griseus, across different environmental/genetic variations. While macromolecular building blocks such as RNA, protein, and lipid composition vary notably, changes in fundamental biomass monomer units such as nucleotides and amino acids are not appreciable. We also observed that flux predictions through FBA is quite sensitive to macromolecular compositions but not the monomer compositions. Based on these observations, we propose ensemble representations of biomass equation in FBA to account for the natural variation of cellular constituents. Such ensemble representations of biomass better predicted the flux through anabolic reactions as it allows for the flexibility in the biosynthetic demands of the cells. The current study clearly highlights that certain component of the biomass equation indeed vary across different conditions, and the ensemble representation of biomass equation in FBA by accounting for such natural variations could avoid inaccuracies that may arise from in silico simulations.

Genome scale metabolic models and analysis for evaluating probiotic potentials.

Probiotics are live beneficial microorganisms that can be consumed in the form of dairy and food products as well as dietary supplements to promote a healthy balance of gut bacteria in humans. Practically, the main challenge is to identify and select promising strains and formulate multi-strain probiotic blends with consistent efficacy which is highly dependent on individual dietary regimes, gut environments, and health conditions. Limitations of current in vivo and in vitro methods for testing probiotic strains can be overcome by in silico model guided systems biology approaches where genome scale metabolic models (GEMs) can be used to describe their cellular behaviors and metabolic states of probiotic strains under various gut environments. Here, we summarize currently available GEMs of microbial strains with probiotic potentials and propose a knowledge-based framework to evaluate metabolic capabilities on the basis of six probiotic criteria. They include metabolic characteristics, stability, safety, colonization, postbiotics, and interaction with the gut microbiome which can be assessed by in silico approaches. As such, the most suitable strains can be identified to design personalized multi-strain probiotics in the future.

NHC-copper-thiophene-2-carboxylate complex for the hydroboration of terminal alkynes.

An air-stable N-heterocyclic carbene-copper thiophene-2-carboxylate (CuTC) complex has been prepared for the stereoselective hydroboration of terminal alkynes using pinacolborane (HBpin) or 1,8-naphthalenediaminatoborane (HBdan). The newly synthesized complex can be directly activated by hydroboranes without a cocatalyst such as a base, and exhibits high reactivity for the hydroboration of alkynes under mild conditions. A gram-scale hydroboration of terminal phenylacetylene demonstrated the applicability of the copper complex for the preparation of alkenyl boronates.

A double blind, placebo-controlled, randomized clinical trial that breast milk derived-Lactobacillus gasseri BNR17 mitigated diarrhea-dominant irritable bowel syndrome.

The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.

Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: a randomized non-inferiority trial.

BACKGROUND: Nefopam is a non-opioid non-steroidal centrally acting analgesic. This study was conducted to assess the analgesic efficacy of intravenous patient-controlled analgesia (IV-PCA) using nefopam alone, compared with a combination of morphine and ketorolac, after laparoscopic gynecologic surgery. METHODS: Sixty patients undergoing laparoscopic gynecologic surgery received IV-PCA. Group A (n = 30) received IV-PCA with a combination of morphine 60 mg and ketorolac 180 mg, while group B (n = 30) received nefopam 200 mg (basal rate 1 ml/h, bolus 1 ml, and lockout time 15 min for both). The primary outcome evaluated was analgesic efficacy using the visual analogue scale (VAS). Other evaluated outcomes included the incidence rate of postoperative nausea and vomiting (PONV), patient satisfaction of pain control, percentage of patients requiring additional opioids, and incidence rate of postoperative adverse effects. RESULTS: Group B was not inferior to group A in relation to the VAS in the post-anesthesia care unit, and at 12, 24, and 48 h after surgery (mean difference [95% confidence interval], 0.50 [-0.43 to 1.43], -0.30 [-1.25 to 0.65], -0.05 [-0.65 to 0.55], and 0.10 [-0.55 to 0.75], respectively). The incidence rate of nausea was lower in group B than in group A at 12 and 24 h after surgery (P = 0.004 and P = 0.017, respectively). There were no significant differences in the other outcomes between groups. CONCLUSIONS: IV-PCA using nefopam alone has a non-inferior analgesic efficacy and produces a lower incidence of PONV in comparison with IV-PCA using a combination of morphine and ketorolac after laparoscopic gynecologic surgery.

Effect of root planing on the reduction of probing depth and the gain of clinical attachment depending on the mode of interproximal bone resorption.

PURPOSE: The purpose of the present study was to evaluate the effect of root planing on the reduction of probing pocket depth and the gain of clinical attachment depending on the pattern of bone resorption (vertical versus horizontal bone loss) in the interproximal aspect of premolar teeth that showed an initial probing pocket depth of 4-6 mm. METHODS: In this study, we analyzed 68 teeth (15 from the maxilla and 53 from the mandible) from 32 patients with chronic periodontitis (17 men and 15 women; mean age, 53.6 years). The probing pocket depth and clinical attachment level at all six sites around each tooth were recorded before treatment to establish a baseline value, and then three months and six months after root planing. RESULTS: The reduction in interdental pocket depth was 1.1 mm in teeth that experienced horizontal bone loss and 0.7 mm in teeth that experienced vertical bone loss. Interdental attachment was increased by 1.0 mm in teeth with horizontal bone loss and by 0.7 mm in teeth with vertical bone loss. The reduction of probing pocket depth and the gain of clinical attachment occurred regardless of defect patterns three and six months after root planing. CONCLUSIONS: The reduction of pocket depth and gain in the clinical attachment level were significantly larger in horizontally patterned interproximal bone defects than in vertical bone defects.

Acoustic improvements after surgical correction in congenital heart disease.

BACKGROUND: Hoarse or asthenic voice is frequently associated with various pediatric cardiac disorders. The aim of this study was to investigate the changes in voice physiology after surgical correction in patients with congenital heart diseases. METHODS: We performed voice analysis using induced crying of 40 infants with congenital heart disease (CHD) such as ventricular septal defect (VSD), patent ductus arteriosus (PDA), and atrial septal defect (ASD; 31 girls, 24 boys; mean age, 11 ± 8.9 months). Cries were serially recorded immediately prior to operation, then 1 week, and 1 month after surgical correction, respectively. Acoustic parameters, fundamental frequency (F0 ), duration of cry, noise to harmonic ratio (NHR), jitter, and shimmer, were extracted using Multi-Dimensional Voice Program™ (MDVP) a computerized speech analysis system. Cries were compared with 30 normal healthy infants of corresponding age. RESULTS: Among the 25 infants with VSD, cry duration, jitter, and shimmer improved after the operation (P < 0.05). F0 and NHR, however, were not significantly different. F0 in patients with PDA improved, but was not statistically significant. The duration of cry, jitter, shimmer, and NHR improved in the PDA group (P < 0.05). The jitter and shimmer parameters improved significantly (P < 0.05), but F0 , cry duration, and NHR in patients with ASD did not show any significant changes. CONCLUSIONS: Deviated voice patterns in pediatric patients with CHD can normalize after surgical correction. In addition, non-invasive analysis such as MDVP can be used to identify vocal paralysis, even in the early postoperative period.

Effects of topiramate on language functions in newly diagnosed pediatric epileptic patients.

BACKGROUND: The aim of this study was to characterize the effects of topiramate on language functions in newly diagnosed pediatric epileptic patients. METHODS: Thirty-eight newly diagnosed epileptic patients were assessed using standard language tests. Data were collected before and after beginning topiramate during which time a monotherapy treatment regimen was maintained. Language tests included the Test of Language Problem Solving Abilities, a Korean version of the Peabody Picture Vocabulary Test. We used language tests in the Korean version because all the patients were spoken Korean exclusively in their families. RESULTS: All the language parameters of Test of Language Problem Solving Abilities worsened after initiation of topiramate (determine cause, 13.2 ± 4.8 to 11.2 ± 4.3; problem solving, 14.8 ± 6.0 to 12.8 ± 5.0; predicting, 9.8 ± 3.6 to 8.8 ± 4.6). Patients given topiramate exhibited a shortened mean length of utterance in words during response (determine cause, 4.8 ± 0.9 to 4.3 ± 0.7; making inference, 4.5 ± 0.8 to 4.1 ± 1.1; predicting, 5.2 ± 1.0 to 4.7 ± 0.6; P < 0.05), provided ambiguous answers during the testing, exhibited difficulty in selecting appropriate words, took more time to provide answers, and used incorrect grammar. However, there were no statistically significant changes in the receptive language of patients after taking topiramate (95.4 ± 20.4 to 100.8 ± 19.1). CONCLUSIONS: Our data suggest that topiramate may have negative effects on problem-solving abilities in children. We recommend performing language tests should be considered in children being treated with topiramate.

Clinical Features of Symptomatic Meckel's Diverticulum in Children: Comparison of Scintigraphic and Non-scintigraphic Diagnosis.

PURPOSE: Meckel's diverticulum (MD) has various clinical manifestations, and diagnosis or selectection of proper diagnostic tools is not easy. This study was conducted in order to assess the clinical differences of MD diagnosed by scintigraphic and non-scintigraphic methods and to find the proper diagnostic tools. METHODS: We conducted a retrospective review ofthe clinical, surgical, radiologic, and pathologic findings of 34 children with symptomatic MD, who were admitted to Gachon University Gil Medical Center, Inha University Hospital, and The Catholic University of Korea, Incheon St. Mary's Hospital between January 2000 and December 2012. The patients were evaluated according to scintigraphic (12 cases; group 1) and non-scintigraphic (22 cases; group 2) diagnosis. RESULTS: The male to female ratio was 7.5: 1. The most frequent chief complaint was lower gastrointestinal (GI) bleeding in group 1 and nonspecific abdominal pain in group 2, respectively. The most frequent pre-operative diagnosis was MD in both groups. Red blood cell (RBC) index was significantly lower in group 1. MD was located at 7 cm to 85cm from the ileocecal valve. Four patients in group 1 had ectopic gastric tissues causing lower GI bleeding. The most frequent treatment modality was diverticulectomy in group 1 and ileal resection in group 2, respectively. CONCLUSION: To diagnose MD might be delayed unless proper diagnostic tools are considered. It is important to understand indications of scintigraphic and non-scintigraphic methods according to clinical and hematologic features of MD. Scintigraphy would be weighed in patients with anemia as well as GI symptoms.

Effect of single-base mutation on activity and folding of 10-23 deoxyribozyme studied by three-color single-molecule ALEX FRET.

We investigated the effect of single-base mutation on the RNA-cleaving activity and ion-induced folding of 10-23 deoxyribozyme at the single-molecule level by 3-color ALEX FRET (alternating laser excitation fluorescence resonance energy transfer). We found that substitution or deletion of a single base in the active region of the enzyme leads to a different folding pathway and enzymatic activity for all three mutants studied, but the severity of the effect was dependent on the type of mutation and the mutation site. We suggest that mutation of even a single base may result in a considerably different ionic and hydrogen-bonding interactions. Structural changes of 10-23 deoxyribozyme as it successively binds with Mg(2+) and the substrate were also unambiguously identified by the current single-molecule-detection method.

Acoustic effects of lamotrigine in pediatric patients with epilepsy.

The aim of this study was to investigate the acoustic effects of lamotrigine in pediatric epileptic patients. Newly diagnosed 52 pediatric epileptic patients were assessed standard speech test through a Computerized Speech Lab applied before the beginning of therapy with lamotrigine and 2months after dosage had been stabilized. The voice onset times for /t/, /k(h)/, /p'/ and /t'/ after the therapy and those for /p/, /k/, /p(h)/, /t(h)/ and /k'/ was not affected. Total durations for all stop consonants did not change significantly except that lenis /p/ and /k/ increased significantly (P<0.05). No noteworthy alteration was observed for mean pitch and speaking rate of counting 1-10. Vowel formants and precise articulation rate remained the same. In conclusion, no significant effects of lamotrigine on speech were found in this study. Lamotrigine is safe for acoustic function in pediatric patients.

Korean speech sound development in children from bilingual Japanese-Korean environments.

PURPOSE: This study investigates Korean speech sound development, including articulatory error patterns, among the Japanese-Korean children whose mothers are Japanese immigrants to Korea. METHODS: The subjects were 28 Japanese-Korean children with normal development born to Japanese women immigrants who lived in Jeonbuk province, Korea. They were assessed through Computerized Speech Lab 4500. The control group consisted of 15 Korean children who lived in the same area. RESULTS: The values of the voice onset time of consonants /p(h)/, /t/, /t(h)/, and /k(*)/ among the children were prolonged. The children replaced the lenis sounds with aspirated or fortis sounds rather than replacing the fortis sounds with lenis or aspirated sounds, which are typical among Japanese immigrants. The children showed numerous articulatory errors for /c/ and /l/ sounds (similar to Koreans) rather than errors on /p/ sounds, which are more frequent among Japanese immigrants. The vowel formants of the children showed a significantly prolonged vowel /o/ as compared to that of Korean children (P<0.05). The Japanese immigrants and their children showed a similar substitution /n/ for /ɧ/ [Japanese immigrants (62.5%) vs Japanese-Korean children (14.3%)], which is rarely seen among Koreans. CONCLUSION: The findings suggest that Korean speech sound development among Japanese-Korean children is influenced not only by the Korean language environment but also by their maternal language. Therefore, appropriate language education programs may be warranted not only or immigrant women but also for their children.