Umbilical Arterial Blood Gas and Perinatal Outcome in the Second Twin according to the Planned Mode of Delivery

Purpose: To compare umbilical arterial gas parameters in the second twin of twin pregnancies according to the mode of deliver

Successful Treatment of Tracheal Stenosis with Slide Tracheoplasty after the Failure of Resection with End-to-End Anastomosis

The combined effects of inhaled irritant gases and heat in burn patients can result in the development of laryngotracheal strictures. Several factors could adversely affect the development of tracheal stenosis and cause the growth of granulation tissue. Yet the current treatment options for this condition are limited because of the paucity of case reports. We report here on a case of a patient who experienced recurrent upper tracheal stenosis after an inhalation injury. She displayed repetitive symptoms of stenosis even after several laryngomicrosurgeries and resection with end-to-end anastomosis. Finally, 5 yr after the burn injury, slide tracheoplasty was successfully performed and the postoperative check-up findings and the increased airway volume seen on imaging were all satisfactory

Immunohistochemical identification and quantitative analysis of cytoplasmic Cu/Zn superoxide dismutase in mouse organogenesis

Cytoplasmic Cu/Zn superoxide dismutase (SOD1) is an antioxidant enzyme that converts superoxide to hydrogen peroxide in cells. Its spatial distribution matches that of superoxide production, allowing it to protect cells from oxidative stress. SOD1 deficiencies result in embryonic lethality and a wide range of pathologies in mice, but little is known about normal SOD1 protein expression in developing embryos. In this study, the expression pattern of SOD1 was investigated in post-implantation mouse embryos and extraembryonic tissues, including placenta, using Western blotting and immunohistochemical analyses. SOD1 was detected in embryos and extraembryonic tissues from embryonic day (ED) 8.5 to 18.5. The signal in embryos was observed at the lowest level on ED 9.5-11.5, and the highest level on ED 17.5-18.5, while levels remained constant in the surrounding extraembryonic tissues during all developmental stages examined. Immunohistochemical analysis of SOD1 expression on ED 13.5-18.5 revealed its ubiquitous distribution throughout developing organs. In particular, high levels of SOD1 expression were observed in the ependymal epithelium of the choroid plexus, ganglia, sensory cells of the olfactory and vestibulocochlear epithelia, blood cells and vessels, hepatocytes and hematopoietic cells of the liver, lymph nodes, osteogenic tissues, and skin. Thus, SOD1 is highly expressed at late stages of embryonic development in a cell- and tissue-specific manner, and can function as an important antioxidant enzyme during organogenesis in mouse embryos

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 µg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 µg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes

A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients

PurposeMucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II.MethodsWe hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-α-iduronate 2-sulphate.ResultsPlasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol·4 hr-1·mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003).ConclusionThese results show that the mild phenotype may be related to residual lysosomal enzyme activity

A pilot study evaluating use of a computer-assisted neurorehabilitation platform for upper-extremity stroke assessment

<p>Abstract</p> <p>Background</p> <p>There is a need to develop cost-effective, sensitive stroke assessment instruments. One approach is examining kinematic measures derived from goal-directed tasks, which can potentially be sensitive to the subtle changes in the stroke rehabilitation process. This paper presents the findings from a pilot study that uses a computer-assisted neurorehabilitation platform, interfaced with a conventional force-reflecting joystick, to examine the assessment capability of the system by various types of goal-directed tasks.</p> <p>Methods</p> <p>Both stroke subjects with hemiparesis and able-bodied subjects used the force-reflecting joystick to complete a suite of goal-directed tasks under various task settings. Kinematic metrics, developed for specific types of goal-directed tasks, were used to assess various aspects of upper-extremity motor performance across subjects.</p> <p>Results</p> <p>A number of metrics based on kinematic performance were able to differentiate subjects with different impairment levels, with metrics associated with accuracy, steadiness and speed consistency showing the best capability. Significant differences were also shown on these metrics between various force field settings.</p> <p>Conclusion</p> <p>The results support the potential of using UniTherapy software with a conventional joystick system as an upper-extremity assessment instrument. We demonstrated the ability of using various types of goal-directed tasks to distinguish between subjects with different impairment levels. In addition, we were able to show that different force fields have a significant effect on the performance across subjects with different impairment levels in the trajectory tracking task. These results provide motivation for studies with a larger sample size that can more completely span the impairment space, and can use insights presented here to refine considerations of various task settings so as to generalize and extend our conclusions.</p

ChIP-chip versus ChIP-seq: Lessons for experimental design and data analysis

<p>Abstract</p> <p>Background</p> <p>Chromatin immunoprecipitation (ChIP) followed by microarray hybridization (ChIP-chip) or high-throughput sequencing (ChIP-seq) allows genome-wide discovery of protein-DNA interactions such as transcription factor bindings and histone modifications. Previous reports only compared a small number of profiles, and little has been done to compare histone modification profiles generated by the two technologies or to assess the impact of input DNA libraries in ChIP-seq analysis. Here, we performed a systematic analysis of a modENCODE dataset consisting of 31 pairs of ChIP-chip/ChIP-seq profiles of the coactivator CBP, RNA polymerase II (RNA PolII), and six histone modifications across four developmental stages of <it>Drosophila melanogaster</it>.</p> <p>Results</p> <p>Both technologies produce highly reproducible profiles within each platform, ChIP-seq generally produces profiles with a better signal-to-noise ratio, and allows detection of more peaks and narrower peaks. The set of peaks identified by the two technologies can be significantly different, but the extent to which they differ varies depending on the factor and the analysis algorithm. Importantly, we found that there is a significant variation among multiple sequencing profiles of input DNA libraries and that this variation most likely arises from both differences in experimental condition and sequencing depth. We further show that using an inappropriate input DNA profile can impact the average signal profiles around genomic features and peak calling results, highlighting the importance of having high quality input DNA data for normalization in ChIP-seq analysis.</p> <p>Conclusions</p> <p>Our findings highlight the biases present in each of the platforms, show the variability that can arise from both technology and analysis methods, and emphasize the importance of obtaining high quality and deeply sequenced input DNA libraries for ChIP-seq analysis.</p

When One Size Does Not Fit All: A Simple Statistical Method to Deal with Across-Individual Variations of Effects

In science, it is a common experience to discover that although the investigated effect is very clear in some individuals, statistical tests are not significant because the effect is null or even opposite in other individuals. Indeed, t-tests, Anovas and linear regressions compare the average effect with respect to its inter-individual variability, so that they can fail to evidence a factor that has a high effect in many individuals (with respect to the intra-individual variability). In such paradoxical situations, statistical tools are at odds with the researcher’s aim to uncover any factor that affects individual behavior, and not only those with stereotypical effects. In order to go beyond the reductive and sometimes illusory description of the average behavior, we propose a simple statistical method: applying a Kolmogorov-Smirnov test to assess whether the distribution of p-values provided by individual tests is significantly biased towards zero. Using Monte-Carlo studies, we assess the power of this two-step procedure with respect to RM Anova and multilevel mixed-effect analyses, and probe its robustness when individual data violate the assumption of normality and homoscedasticity. We find that the method is powerful and robust even with small sample sizes for which multilevel methods reach their limits. In contrast to existing methods for combining p-values, the Kolmogorov-Smirnov test has unique resistance to outlier individuals: it cannot yield significance based on a high effect in one or two exceptional individuals, which allows drawing valid population inferences. The simplicity and ease of use of our method facilitates the identification of factors that would otherwise be overlooked because they affect individual behavior in significant but variable ways, and its power and reliability with small sample sizes (<30–50 individuals) suggest it as a tool of choice in exploratory studies

DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use