Frequent Use of Fresh Frozen Plasma Is a Risk Factor for Venous Thrombosis in Extremely Low Birth Weight Infants: A Matched Case-control Study

Percutaneously inserted central catheters (PICCs) are often used in neonatal medicine. Venous thrombosis (VT) is one of the complications associated with PICC use. According to some reports, fresh frozen plasma (FFP) may be a risk factor for VT. The purpose of this study was to determine whether FFP use is associated with VT in extremely low birth weight infants (ELBWIs). We performed a matched case-control study on risk factors for VT in ELBWIs born over a period of 5 years in the neonatal intensive care unit of a tertiary hospital. Controls were infants from the unit matched for gestational age and birth weight. We performed univariate analyses and created receiver operating characteristic (ROC) curves for the cut-off values of continuous parameters such as FFP. We also conducted multivariate conditional logistic regression analysis and calculated adjusted odds ratios and their 95% confidence intervals. Thirteen VT cases and 34 matched controls were examined. Using an ROC curve, FFP by day 5＞50mL/kg was selected as the cut-off value. In multivariate conditional logistic regression analysis, FFP by day 5＞50mL/kg exhibited an adjusted odds ratio of 5.88 (95% confidence interval:1.12-41.81, p＝0.036). FFP by day 5＞50mL/kg may be a risk factor for VT in ELBWIs

Risk Factors for Nosocomial Infection in the Neonatal Intensive Care Unit by the Japanese Nosocomial Infection Surveillance (JANIS)

We evaluated the infection risks in the neonatal intensive care unit (NICU) using data of NICU infection surveillance data. The subjects were 871 NICU babies, consisting of 465 boys and 406 girls, who were cared for between June 2002 and January 2003 in 7 medical institutions that employed NICU infection surveillance. Infections were defined according to the National Nosocomial Infection Surveillance (NNIS) System. Of the 58 babies with nosocomial infections, 15 had methicillin-resistant Staphylococcus aureus (MRSA) infection. Multiple logistic regression analysis demonstrated that the odds ratio for nosocomial infections was significantly related to gender, birth weight and the insertion of a central venous catheter (CVC). When the birth weight group of more than 1, 500g was regarded as the reference, the odds ratio was 2.35 in the birth weight group of 1,000-1,499g and 8.82 in the birth weight group of less than 1,000g. The odds ratio of the CVC () for nosocomial infection was 2.27. However, other devices including artificial ventilation, umbilical artery catheter, umbilical venous catheter, and urinary catheter were not significant risk factors. The incidence of MRSA infection rapidly increased from 0.3% in the birth weight group of more than 1,500g to 2.1% in the birth weight group of 1,000-1,499g, and to 11.1% in the birth weight group of less than 1,000g. When the birth weight group of more than 1,500g was regarded as the reference, multiple logistic regression analysis demonstrated that the odds ratio was 7.25 in the birth weight group of 1,000-1,499g and 42.88 in the birth weight group of less than 1,000g. These odds ratios were significantly higher than that in the reference group. However, the application of devices did not cause any significant differences in the odds ratio for MRSA infection.</p

In-situ micro Raman studies on graphitic carbon in some Antarctic ureilites

The fine structures of graphitic materials contained in four Antarctic ureilites (ALH-77257,ALH-78019,MET-78008 and Y-791538) were investigated using a laser light (514.5nm), which could be focused onto a spot of 1μm in diameter. Raman spectra obtained differ not only among individual ureilite samples, but also among positions within a single carbonaceous vein of the same specimen. Moreover, one can classify the carbon into several groups on the basis of the spectra concerned. For all samples, both well-ordered graphitic carbon and semi-ordered graphitic carbon were observed. Amorphous carbon was detected in ALH-77257 and MET-78008. The difference in structural ordering among the samples is attributed to the difference in distribution of the components of carbonaceous material, indicating minor difference in genetic conditions or in locality within the parent body. Structural heterogeneity of carbon within a single carbonaceous vein implies the occurrence of two (or three) types of carbonaceous matters which have fairly different physicochemical properties and distinct histories. For the genesis of the carbonaceous matter in ureilites, a two-stage model is proposed assuming the graphite crystallization from metallic phase followed by the inflow of semi-ordered graphitic carbon or amorphous carbon into the well-ordered graphitic carbon produced from the metal

Control Technique of Maximum Local Lyapunov Exponent on Stable Periodic Solution in Continuous-Time Non-Autonomous Dynamical Systems

We previously proposed a parametric controller to avoid undesirable bifurcations of stable fixed and periodic points in discrete-time dynamical systems. The parameter regulation is derived from an optimization problem on the maximum local Lyapunov exponent and a method of steepest descent. In this paper, on the basis of the ideas and a stroboscopic mapping that transforms the trajectory of a continuous-time periodic solution into a sequence of points, we propose a technique to control the maximum local Lyapunov exponent on stable periodic oscillations in continuous-time non-autonomous dynamical systems

Itinerant memory dynamics and global bifurcations in chaotic neural networks

We have considered itinerant memory dynamics in a chaotic neural network composed of four chaotic neurons with synaptic connections determined by two orthogonal stored patterns as a simple example of a chaotic itinerant phenomenon in dynamical associative memory. We have analyzed a mechanism of generating the itinerant memory dynamics with respect to intersection of a pair of ␣ branches of periodic points and collapse of a periodic in-phase attracting set. The intersection of invariant sets is numerically verified by a novel method proposed in this paper. 3,11,12 Among such studies we focus on the associative memory dynamics in this paper. Adachi and Aihara analyzed the dynamics of associative memory networks composed of chaotic neurons in detail and examined characteristics of the retrieval process

A KDM6 inhibitor potently induces ATF4 and its target gene expression through HRI activation and by UTX inhibition

UTX/KDM6A encodes a major histone H3 lysine 27 (H3K27) demethylase, and is frequently mutated in various types of human cancers. Although UTX appears to play a crucial role in oncogenesis, the mechanisms involved are still largely unknown. Here we show that a specific pharmacological inhibitor of H3K27 demethylases, GSK-J4, induces the expression of transcription activating factor 4 (ATF4) protein as well as the ATF4 target genes (e.g. PCK2, CHOP, REDD1, CHAC1 and TRIB3). ATF4 induction by GSK-J4 was due to neither transcriptional nor post-translational regulation. In support of this view, the ATF4 induction was almost exclusively dependent on the heme-regulated eIF2α kinase (HRI) in mouse embryonic fibroblasts (MEFs). Gene expression profiles with UTX disruption by CRISPR-Cas9 editing and the following stable re-expression of UTX showed that UTX specifically suppresses the expression of the ATF4 target genes, suggesting that UTX inhibition is at least partially responsible for the ATF4 induction. Apoptosis induction by GSK-J4 was partially and cell-type specifically correlated with the activation of ATF4-CHOP. These findings highlight that the anti-cancer drug candidate GSK-J4 strongly induces ATF4 and its target genes via HRI activation and raise a possibility that UTX might modulate cancer formation by regulating the HRI-ATF4 axis

Coordinated elevation of membrane type 1-matrix metalloproteinase and matrix metalloproteinase-2 expression in rat uterus during postpartum involution

BACKGROUND: The changes occurring in the rodent uterus after parturition can be used as a model of extensive tissue remodeling. As the uterus returns to its prepregnancy state, the involuting uterus undergoes a rapid reduction in size primarily due to the degradation of the extracellular matrix, particularly collagen. Membrane type-I matrix metalloproteinase (MT1-MMP) is one of the major proteinases that degrades collagen and is the most abundant MMP form in the uterus. Matrix metalloproteinase-2(MMP-2) can degrade type I collagen, although its main function is to degrade type IV collagen found in the basement membrane. To understand the expression patterns of matrix metalloproteinases (MMPs) in the rat uterus, we analyzed their activities in postpartum uterine involution. METHODS: We performed gelatin zymography, northern blot analysis and immunohistochemistry to compare the expression levels of MT1-MMP, MMP-2, matrix metalloproteinase-9 (MMP-9) and the tissue inhibitors of MMPs-1 and 2 (TIMP-1 and TIMP-2) in the rat uterus 18 h, 36 h and 5 days after parturition with their expression levels during pregnancy (day 20). RESULTS: We found that both MT1-MMP and MMP-2 localized mainly in the cytoplasm of uterine interstitial cells. The expression levels of MT1-MMP and MMP-2 mRNAs and the catalytic activities of the expressed proteins significantly increased 18 h and 36 h after parturition, but at postpartum day 5, their mRNA expression levels and catalytic activities decreased markedly. The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2. CONCLUSION: These expression patterns indicate that MT1-MMP, MMP-2, MMP-9, TIMP-1 and TIMP-2 may play key roles in uterine postpartum involution and subsequent functional regenerative processes

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats

<p>Abstract</p> <p>Background</p> <p>Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.</p> <p>Methods</p> <p>In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).</p> <p>Results</p> <p>Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.</p> <p>Conclusions</p> <p>Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.</p

Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration

Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation