Changes to Gut Microbiota Following Systemic Antibiotic Administration in Infants.

Long-term antibiotic use can have consequences on systemic diseases, such as obesity, allergy, and depression, implicating the causal role of gut microbiome imbalance. However, the evaluation of the effect of antibiotics in early infancy on alterations to the gut microbiome remains poorly understood. This study aimed to evaluate the gut microbiome state in infancy following systemic antibiotic treatment. Twenty infants under 3 months of age who had received antibiotics for at least 3 days were enrolled, and their fecal samples were collected 4 weeks after antibiotic administration finished. Thirty-four age-matched healthy controls without prior exposure to antibiotics were also assessed. The relative bacterial abundance in feces was obtained via sequencing of 16 S rRNA genes, and alpha and beta diversities were evaluated. At the genus level, the relative abundance of Escherichia/Shigella and Bifidobacterium increased (p = 0.03 and p = 0.017, respectively) but that of Bacteroides decreased (p = 0.02) in the antibiotic treatment group. The microbiome of the antibiotic treatment group exhibited an alpha diversity lower than that of the control group. Thus, systemic antibiotic administration in early infancy affects the gut microbiome composition even after a month has passed; long-term studies are needed to further evaluate this.

Is High Milk Intake Good for Children's Health? A National Population-Based Observational Cohort Study.

Milk is widely considered as a beneficial product for growing children. This study was designed to describe the milk consumption status of Korean children aged 30-36 months and to investigate its association with the risk of obesity and iron deficiency anemia (IDA). This nationwide administrative study used data from the Korean national health insurance system and child health screening examinations for children born in 2008 and 2009. In total, 425,583 children were included, and they were divided into three groups based on daily milk consumption: low milk group (do not drink or drink <200 mL milk per day, n = 139,659), reference group (drink 200-499 mL milk per day, n = 255,670), and high milk group (drink ≥500 mL milk per day, n = 30,254). After adjusting variable confounding factors, the consumption of a large amount of milk of ≥500 mL per day at the age of 30-36 months was associated with an increased risk of obesity at the age of 42-72 months and IDA after the age of 30 months. These results may provide partial evidence for dietary guidelines for milk consumption in children that are conducive to health.

Epidemiological Investigation of Tick Species from Near Domestic Animal Farms and Cattle, Goat, and Wild Boar in Korea.

This study aimed to investigate the tick species and give background for tick-borne investigations in Korea. Ticks were collected from the area within 2 km radius of the 4 domestic animal farms, where they were located in mountainous areas and raising animals on pasture, and from animal bodies in 2014 and 2015. In total, 7,973 nymphal and adult ticks were collected from the farms - 7,758 Haemaphysalis longicornis, 198 Haemaphysalis flava, and 17 Ixodes nipponensis, and 1,763 were collected from animals - 729 H. longicornis from cattle; 569 H. longicornis from goats; and 297 H. longicornis, 118 H. flava, 1 I. nipponensis, and 49 Amblyomma testudinarium from wild boars. As more species of ticks were collected from wild boars than domesticated animals and their habitats, various animal hosts should be considered while investigating tick species.

The natural history of fetal diagnosed isolated ventricular septal defect.

OBJECTIVE: This study was undertaken to clarify the natural course of ventricular septal defect, and to find an index that would help in prenatal counseling. METHODS: Between January 2010 and December 2014, 18 188 fetuses underwent echocardiographic examinations. Of these, 228 isolated ventricular septal defect cases were retrospectively reviewed. RESULTS: In this retrospective study, the incidence of isolated ventricular septal defect was 1.25% (228/18 188). There were 146 patients who underwent echocardiography after delivery in order to confirm the natural course of patients with isolated ventricular septal defect. Of the 146 cases, 64 cases (43.84%) had the ventricular septal defect naturally closed in the fetal period. Of the 82 patients with ventricular septal defect at birth, 25 patients showed natural closure during follow-up. However, four patients (2.74%) required surgical treatment for ventricular septal defect. In case of perimembranous defects, natural closure is more frequent in the fetal period than in the postnatal period. CONCLUSION: Our results indicate that 60.96% (89/146) of isolated ventricular septal defects diagnosed during the fetal life are closed naturally. Perimembranous type defect, small defect (<2 mm) and maternal age less than 35 years are the good prognostic factors for the natural closure during fetal life. © 2017 John Wiley & Sons, Ltd.

Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants.

BACKGROUND: To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. METHODS: Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. RESULTS: Pharmacological closures were attempted at postnatal day 2-3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . CONCLUSION: We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function.

Molecular detection of severe fever with thrombocytopenia syndrome virus (SFTSV) in feral cats from Seoul, Korea.

This study tested serum samples of feral cats from a highly urbanized habitat, Seoul, Korea to determine the infection to severe fever with thrombocytopenia syndrome virus (SFTSV). From 126 samples tested, SFTSV was detected by RT-PCR in 22 (17.5%) cats from various sites of Seoul. Sequences identified from this study were grouped with clusters from China and Japan. Our result provides data that SFTSV may have been circulating in settings that were suspected to have relatively low risk, such as highly urbanized habitats. Thus it warrants further study to investigate the ecology of SFTSV in urban-dwelling animals including ticks, human and other potential host species.

Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity-related insulin resistance in adolescents.

PURPOSE: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. METHODS: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the participants was 12.9±0.3 years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (7.8±1.9 µg/mL vs. 6.0±1.6 µg/mL, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. CONCLUSION: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

Acute hyponatremia with seizure and mental change after oral sodium picosulfate/magnesium citrate bowel preparation.

Sodium picosulfate/magnesium citrate (Picolight Powder), which is used as a bowel preparation for the colon and the rectum, can cause a severe electrolyte imbalance like hyponatremia. When hyponatremia gets severe or occurs rapidly, it can lead to death due to associated complications. We have experienced a case of hyponatremia associated with seizure and loss of consciousness in a 76-year-old woman, who took sodium picosulfate/magnesium citrate as a bowel preparation for colonoscopy. She was taking thiazide and synthroid for the treatment of hypertension and hypothyroidism, respectively, and she had other underlying medical conditions such as a history of seizure and dementia. Following the diagnosis of hyponatremia, we used an intravenous injection of 3% NaCl to normalize the sodium level in her serum, and her associated symptoms soon disappeared.

Inverted-takotsubo cardiomyopathy in a patient with pulmonary embolism.

As the use of early coronary angiography and echocardiography become widely available in the setting of acute coronary syndrome, the gradual increase for variant forms of transient left ventricular (LV) apical ballooning syndrome have been recognized. This syndrome usually occurs in women and is frequently elicited by an intense emotional, psychological, and physical event. While the patients' characteristics between typical and non-typical LV ballooning syndrome seem to differ, the presentation, clinical features, and reversibility of LV wall motion abnormalities are similar. We present a middle-aged woman who experienced inverted takotsubo cardiomyopathy triggered by pulmonary embolism. To the best of our knowledge, this case is particularly unique and is rarely reported in the disease entity.

Characterization of estrogen-responsive transgenic marine medaka Oryzias dancena germlines harboring red fluorescent protein gene under the control by endogenous choriogenin H promoter.

Transgenic marine medaka (Oryzias dancena) germlines were generated by the microinjection of the red fluorescent protein (RFP) reporter gene (rfp) driven by the endogenous choriogenin H gene (chgH) promoter. The selected transgenic lines contained multiple copies of the transgene (3-42 copies per cell) in their genomes. Although all the founders were mosaic, the transgene was stably transmitted from the F1 generation to all subsequent generations following a Mendelian pattern. Different transgenic lines showed different responsiveness to estradiol-17ß (E2) exposure at the mRNA and protein levels, and the expression efficiency was dependent upon the transgene copy number. The induction of RFP was significantly affected by the developmental stage of transgenic larvae: later-stage larvae (older than 7 days post-hatching) showed higher sensitivity to E2 exposure than earlier-stage larvae. The response of transgenic expression to E2 was fairly dependent upon the E2 dose (200-3,200 ng/L) and exposure period (1-7 days), according to both a microscopic examination of RFP intensity and a qRT-PCR assay. The transgenic marine medaka showed similar transgenic responses to E2 under freshwater, brackish, and seawater conditions. In addition to E2, the transgenic RFP signal was also successfully induced during 1-week exposure to various other natural (1 µg/L estrone and 10 µg/L estriol) and synthetic (xeno)estrogens (0.1 µg/L 17α-ethynylestradiol, 1 µg/L diethylstilbestrol, and 10 mg/L bisphenol A). The efficiency of transgene expression varied greatly among the chemicals tested. The results of this study suggest that the chgH-rfp transgenic marine medaka species will be useful in the in vivo detection of waterborne estrogens under a wide range of salinity conditions.

Characterization of stable fluorescent transgenic marine medaka (Oryzias dancena) lines carrying red fluorescent protein gene driven by myosin light chain 2 promoter.

Stable transgenic germlines carrying the red fluorescence protein (RFP) gene (rfp) driven by fast skeletal myosin light chain-2 gene (mlc2f) promoter were established in a truly euryhaline fish species, the marine medaka (Oryzias dancena; Beloniformes). Transgenic lines contained transgene copy numbers varying from a single copy to more than 230 copies per genome. Although the transgenic founders displayed mosaic and/or ectopic expression of the RFP signal, the resultant F1 transgenics and their progeny showed consistently stable transmission of the transgenic locus and uniform RFP signal through several subsequent generations. In adult transgenics, an authentic brilliant red fluorescence was achieved over the skeletal muscles of the transgenic individuals, which might be sufficient for ornamental display. Expression analysis of the transgenic mRNAs indicated that rfp transcripts were predominantly expressed in the skeletal muscles. Different transgenic lines displayed different levels of transgene expression at the mRNA, protein, and phenotypic levels. However, the efficiency of transgene expression was independent of the transgene copy number. The RFP protein levels were consistently stable in the transgenic fish muscles through several generations, up to F5. The results of this study suggest that transgenic marine medaka that acquire strong fluorescent signals in their skeletal muscles can be developed as a promising, novel ornamental fish for display in both freshwater and seawater aquaria.

Modulation of warm-temperature-acclimation-associated 65-kDa protein genes (Wap65-1 and Wap65-2) in mud loach (Misgurnus mizolepis, Cypriniformes) liver in response to different stimulatory treatments.

Two paralogous isoform cDNAs of warm-temperature-acclimation-associated 65-kDa protein (Wap65-1 and Wap65-2) were isolated from the cypriniform species, mud loach (Misgurnus mizolepis), and characterized. The deduced amino acid sequences of the two mud loach Wap65 isoforms (mlWap65-1 and mlWap65-2) share moderate levels of sequence homology with their corresponding orthologues from teleosts and with human hemopexin, a possible mammalian homologue. Both isoforms display conserved features, including essential motifs and/or residues that are important for the protein structure of hemopexin. In overall, mlWap65-2 is more homologous to human hemopexin than is mlWap65-1. Both mud loach Wap65 transcripts are predominantly expressed in liver, although the transcripts are ubiquitously detectable in most tissues with variable basal expression. Both mlWap65 isoforms are differentially regulated during embryonic development, and the changes in transcript levels during embryogenesis are greater for mlWap65-2 than for mlWap65-1. The transcription of the mlWap65 genes is differentially modulated by various stimuli, including thermal changes, immune challenge (lipopolysaccharide injection or bacterial infection), and heavy metal exposure (cadmium, copper, or nickel). The isoform mlWap65-1 is more responsive to warm temperature treatments than mlWap65-2, whereas mlWap65-2 is much more strongly stimulated by immune and heavy metal challenges than is mlWap65-1. Taken together, the results of this study suggest that mud loach Wap65 isoforms are potentially involved in multiple cellular pathways and that the two mud loach Wap65 isoforms undergo functional partitioning or subfunctionalization.

Investigation of the electric field components of tDCS via anisotropically conductive gyri-specific finite element head models.

Transcranial Direct Current Stimulation (tDCS) is considered as one of the promising techniques for noninvasive brain stimulation and brain disease therapy. In this study, we have investigated the effect of skull and white matter (WM) anisotropy on the induced electric field (EF) by tDCS in two different montages; one using a pair of clinically used rectangular pad electrodes and the other 4(cathodes)+1(anode) ring electrodes. Using a gyri-specific finite element (FE) head model, we simulated tDCS and investigated the radial and tangential components of the induced EF in terms of their distribution over the cortical surface besides the distribution of the transverse and longitudinal components within WM. The results show that the tangential component of the EF on the cortical surface seems to be the main cause of the cortical stimulation of tDCS. Also WM anisotropy seems to increase the dispersion of the transverse component of the EF that affects the dispersion of the EF magnitude within the WM region.

Molecular characterization of hepcidin gene from mud loach (Misgurnus mizolepis; Cypriniformes).

The gene encoding hepcidin, an antimicrobial peptide, was isolated and characterized in the mud loach Misgurnus mizolepis (Cypriniformes). Mud loach hepcidin shows a considerable degree of structural homology to other vertebrate hamp1 orthologues at both the gene and protein levels, particularly with respect to its tripartite genomic organization, typical transcription-factor-binding motifs in its promoter, and conserved cysteine residues in the mature cationic peptide. The mud loach possesses at least two allelic forms of hamp1, which are expected to be translated into the same hepcidin preproprotein. The two alleles are transmitted from parental fish to offspring with a Mendelian inheritance pattern, as demonstrated with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. Southern blot hybridization analysis showed a high degree of polymorphisms in the restriction patterns of individuals. Mud loach hamp1 mRNA is predominantly expressed in the liver, although many other tissues showed detectable levels of hamp1 transcripts in RT-PCR assay. Lipopolysaccharide and bacterial challenges induced significant hamp1 expression, whereas hamp1 was not clearly stimulated by polyinosinic:polycytidylic acid [poly(I:C)] injection. Iron overload and Cu exposure also elevated hamp1 transcripts in various tissues. The transcriptional activation of mud loach hamp1 in response to these stimuli varied among tissue types, and the liver appears predominantly involved in hepcidin-mediated iron regulation. However, hepcidin expression in the kidney and spleen was preferentially modulated by inflammation-mediated signals produced by immune challenges. Our results suggest that mud loach hepcidin has two basic functions, in iron regulation and antimicrobial activity, and that its transcription is also modulated by other environmental perturbations, including heavy metal exposure.

Functional ability of cytoskeletal ß-actin regulator to drive constitutive and ubiquitous expression of a fluorescent reporter throughout the life cycle of transgenic marine medaka Oryzias dancena.

Marine medaka Oryzias dancena, a candidate model organism, represents many attractive merits as a material for experimental transgenesis and/or heterologous expression assay particularly in the field of ecotoxicology and developmental biology. In this study, cytoskeletal ß-actin gene was characterized from O. dancena and the functional capability of its promoter to drive constitutive expression of foreign reporter protein was evaluated. The O. dancena ß-actin gene possessed a conserved genomic organization of vertebrate major cytoplasmic actin genes and the bioinformatic analysis of its 5'-upstream regulatory region predicted various transcription factor binding motifs. Heterologous expression assay using a red fluorescent protein (RFP) reporter construct driven by the O. dancena ß-actin regulator resulted in stunningly bright expression of red fluorescence signals in not only microinjected embryos but also grown-up transgenic adults. Although founder transgenics exhibited mosaic patterns of RFP expression, transgenic offspring in subsequent generations displayed a vivid and uniform expression of RFP continually from embryos to adults. Based on the blot hybridization assays, two transgenic lines established in this study were proven to possess high copy numbers of transgene integrants (approximately 240 and 34 copies, respectively), and the transgenic genotype in both lines could successfully be passed stably up to three generations, although the rate of transgene transmission in one of the two transgenic lines was significantly lower than expected Mendelian ratio. Significant red fluorescence color could be ubiquitously observable in all the tissues or organs of the transgenics. Quantitative real-time RT-PCR represented that the expression pattern of transgene under the regulation of ß-actin promoter would resemble, in overall, the regulation of endogenous ß-actin gene in adult tissues, although putative mechanism for competitive or independent regulation between transgene and endogenous gene could also be found in several tissues. Results from this study undoubtedly indicate that the O. dancena ß-actin promoter would be powerful enough to fluorescently visualize most cell types in vivo throughout its whole lifespan. This study could be a useful start point for a variety of transgenic experiments with this species concerning the constitutive expression of living fluorescent color reporters and other foreign proteins.

TMS modeling toolbox for realistic simulation.

Transcranial magnetic stimulation (TMS) is a technique for brain stimulation using rapidly changing magnetic fields generated by coils. It has been established as an effective stimulation technique to treat patients suffering from damaged brain functions. Although TMS is known to be painless and noninvasive, it can also be harmful to the brain by incorrect focusing and excessive stimulation which might result in seizure. Therefore there is ongoing research effort to elucidate and better understand the effect and mechanism of TMS. Lately Boundary element method (BEM) and Finite element method (FEM) have been used to simulate the electromagnetic phenomenon of TMS. However, there is a lack of general tools to generate the models of TMS due to some difficulties in realistic modeling of the human head and TMS coils. In this study, we have developed a toolbox through which one can generate high-resolution FE TMS models. The toolbox allows creating FE models of the head with isotropic and anisotropic electrical conductivities in five different tissues of the head and the coils in 3D. The generated TMS model is importable to FE software packages such as ANSYS for further and efficient electromagnetic analysis. We present a set of demonstrative results of realistic simulation of TMS with our toolbox.

Reduced spatial focality of electrical field in tDCS with ring electrodes due to tissue anisotropy.

For effective stimulation with tDCS, spatial focality of induced electrical field (EF) is one of the important factors to be considered. Recently, there have been some studies to improve the spatial focality via different types of electrodes and their new configurations: some improvements using ring electrodes were reported over the conventional pad electrodes. However, most of these studies assumed isotropic conductivities in the head. In this work, we have investigated the effect of tissue anisotropy on the spatial focality of tDCS with the 4+1 ring electrode configuration via a 3-D high-resolution finite element (FE) head model with anisotropic conductivities in the skull and white matter. By examining the profiles of the induced EF from the head models with isotropic and anisotropic conductivities respectively, we found that the spatial focality of the induced EF significantly drops and get diffused due to tissue anisotropy. Our analysis suggests that it is critical to incorporate tissue anisotropy in the stimulation of the brain via tDCS.

A single tri-axial accelerometer-based real-time personal life log system capable of activity classification and exercise information generation.

Recording a personal life log (PLL) of daily activities is an emerging technology for u-lifecare and e-health services. In this paper, we present an accelerometer-based personal life log system capable of human activity classification and exercise information generation. In our system, we use a tri-axial accelerometer and a real-time activity recognition scheme in which a set of augmented features of accelerometer signals, processed with Linear Discriminant Analysis (LDA), is classified by our hierarchical artificial neural network classifier: in the lower level of the classifier, a state of an activity is recognized based on the statistical and spectral features; in the upper level, an activity is recognized with a set of augmented features including autoregressive (AR) coefficients, signal magnitude area (SMA), and tilt angles (TA). Upon the recognition of each activity, we further estimate exercise information such as energy expenditure based on Metabolic Equivalents (METS), step count, walking distance, walking speed, activity duration, etc. Our PLL system functions in real-time and all information generated from our system is archived in a daily-log database. By testing our system on seven different daily activities, we have obtained an average accuracy of 84.8% in activity recognition and generated their relative exercise information.

Genomic organization and mRNA expression of manganese superoxide dismutase (Mn-SOD) from Hemibarbus mylodon (Teleostei, Cypriniformes).

The genomic structure of manganese superoxide dismutase (Mn-SOD) was characterized in Hemibarbus mylodon (Teleostei, Cypriniformes), an endangered freshwater fish species, and changes in Mn-SOD mRNA expression in response to various stimuli, such as challenge with lipopolysaccharide (LPS), bacteria, or heavy metals, were examined. H. mylodon Mn-SOD possesses well-conserved features of vertebrate Mn-SODs, including its homologous quinquepartite gene structure (five exons interrupted by four introns) and high sequence identity with vertebrate orthologs in coding regions, including a typical eukaryotic Mn-SOD signature. The 5'-regulatory upstream region of the H. mylodon Mn-SOD gene lacked a canonical TATA sequence; however, it displayed various transcription factor binding elements that may be involved in immune and stress responses, as well as the modulation of enzymes that mediate the metabolism of metals and other xenobiotics. Bioinformatic analysis of Mn-SOD genes from fish and mammalian genome databases revealed chromosomal synteny of the Mn-SOD locus in the vertebrate lineage. Mn-SOD transcripts were ubiquitously detected in diverse tissues with variable levels of basal expression using an RT-PCR assay. Mn-SOD expression in the liver and kidney were significantly modulated by injection of LPS (1, 5, or 10 microg g(-1) body weight), Edwardsiella tarda challenge (5 x 10(3) or 5 x 10(5) cells/fish), and heavy metal exposure (Cd, Cu, or Zn at 5 microM). Results from this study suggest that Mn-SOD plays an important role in the host defence against oxidative damage caused by infection-mediated inflammation and/or toxicant related stress in this species.