Dynamic Changes in Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis with Respect to Antibiotic Susceptibility

Young Woo Um,1 Inwon Park,1 Jae Hyuk Lee,1 Hee Eun Kim,1 Dongkwan Han,1 Seung Hyun Kang,1 Seonghye Kim,1 You Hwan Jo1– 3 1Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 2Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea; 3Disaster Medicine Research Center, Seoul National University Medical Research Center, Seoul, KoreaCorrespondence: Jae Hyuk Lee, Department of Emergency Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea, Tel +82-31-787-7579, Fax +82-31-787-4055, Email [email protected]: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis.Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility.Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028).Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.Keywords: anti-bacterial agents, biomarkers, drug resistance, sepsis, triggering receptor expressed on myeloid cells-

Thoracoscopic-assisted repair of a bochdalek hernia in an adult: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bochdalek hernia is a congenital defect of the diaphragm that usually presents in the neonatal period with life-threatening cardiorespiratory distress. It is rare for Bochdalek hernias to remain silent until adulthood. Once a Bochdalek hernia has been diagnosed, surgical treatment is necessary to avoid complications such as perforation and necrosis.</p> <p>Case presentation</p> <p>We present a 17-year-old Japanese boy with left-upper-quadrant pain for two months. Chest radiography showed an elevated left hemidiaphragm. Computed tomography revealed a congenital diaphragmatic hernia. The spleen and left colon had been displaced into the left thoracic cavity through a left posterior diaphragmatic defect. We diagnosed a Bochdalek hernia. Surgical treatment was performed via a thoracoscopic approach. The boy was placed in the reverse Trendelenburg position and intrathoracic pressure was increased by CO₂gas insufflations. This is a very useful procedure for reducing herniated contents and we were able to place the herniated organs safely back in the peritoneal cavity. The diaphragmatic defect was too large to close with thoracoscopic surgery alone. Small incision thoracotomy was required and primary closure was performed. His postoperative course was uneventful and there has been no recurrence of the diaphragmatic hernia to date.</p> <p>Conclusion</p> <p>Thoracoscopic surgery, performed with the boy in the reverse Trendelenburg position and using CO₂gas insufflations in the thoracic cavity, was shown to be useful for Bochdalek hernia repair.</p

Histone arginine methylation regulates pluripotency in the early mouse embryo

It has been generally accepted that the mammalian embryo starts its development with all cells identical, and only when inside and outside cells form do differences between cells first emerge. However, recent findings show that cells in the mouse embryo can differ in their developmental fate and potency as early as the four-cell stage1,2,3,4. These differences depend on the orientation and order of the cleavage divisions that generated them2,5. Because epigenetic marks are suggested to be involved in sustaining pluripotency6,7, we considered that such developmental properties might be achieved through epigenetic mechanisms. Here we show that modification of histone H3, through the methylation of specific arginine residues, is correlated with cell fate and potency. Levels of H3 methylation at specific arginine residues are maximal in four-cell blastomeres that will contribute to the inner cell mass (ICM) and polar trophectoderm and undertake full development when combined together in chimaeras. Arginine methylation of H3 is minimal in cells whose progeny contributes more to the mural trophectoderm and that show compromised development when combined in chimaeras. This suggests that higher levels of H3 arginine methylation predispose blastomeres to contribute to the pluripotent cells of the ICM. We confirm this prediction by overexpressing the H3-specific arginine methyltransferase CARM1 in individual blastomeres and show that this directs their progeny to the ICM and results in a dramatic upregulation of Nanog and Sox2. Thus, our results identify specific histone modifications as the earliest known epigenetic marker contributing to development of ICM and show that manipulation of epigenetic information influences cell fate determination

Dietary behavior and knowledge of dental erosion among Chinese adults

<p>Abstract</p> <p>Objectives</p> <p>To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong.</p> <p>Methods</p> <p>Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion.</p> <p>Results</p> <p>A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries.</p> <p>Conclusion</p> <p>Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.</p

Induction of Interferon-Stimulated Genes by Chlamydia pneumoniae in Fibroblasts Is Mediated by Intracellular Nucleotide-Sensing Receptors

BACKGROUND: Recognition of microorganisms by the innate immune system is mediated by pattern recognition receptors, including Toll-like receptors and cytoplasmic RIG-I-like receptors. Chlamydia, which include several human pathogenic species, are obligate intracellular gram-negative bacteria that replicate in cytoplasmic vacuoles. The infection triggers a host response contributing to both bacterial clearance and tissue damage. For instance, type I interferons (IFN)s have been demonstrated to exacerbate the course of Chlamydial lung infections in mice. METHODS/PRINCIPAL FINDINGS: Here we show that Chlamydia pneumoniae induces expression of IFN-stimulated genes (ISG)s dependent on recognition by nucleotide-sensing Toll-like receptors and RIG-I-like receptors, localized in endosomes and the cytoplasm, respectively. The ISG response was induced with a delayed kinetics, compared to virus infections, and was dependent on bacterial replication and the bacterial type III secretion system (T3SS). CONCLUSIONS/SIGNIFICANCE: Activation of the IFN response during C. pneumoniae infection is mediated by intracellular nucleotide-sensing PRRs, which operate through a mechanism dependent on the bacterial T3SS. Strategies to inhibit the chlamydial T3SS may be used to limit the detrimental effects of the type I IFN system in the host response to Chlamydia infection

The Ubiquitin Peptidase UCHL1 Induces G0/G1 Cell Cycle Arrest and Apoptosis Through Stabilizing p53 and Is Frequently Silenced in Breast Cancer

Background: Breast cancer (BrCa) is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1) is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear. Methodology/Principal Findings: We found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90%) and 53 of 66 (80%) primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90Sexpressed cells

Manipulation of Signaling Thresholds in “Engineered Stem Cell Niches” Identifies Design Criteria for Pluripotent Stem Cell Screens

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate. Herein we use mouse embryonic stem cells (mESC) and micro-contact printing (µCP) to investigate how niche size controls endogenous signaling thresholds. µCP is used to restrict colony diameter, separation, and degree of clustering. We show, for the first time, spatial control over the activation of the Janus kinase/signal transducer and activator of transcription pathway (Jak-Stat). The functional consequences of this niche-size-dependent signaling control are confirmed by demonstrating that direct and indirect transcriptional targets of Stat3, including members of the Jak-Stat pathway and pluripotency-associated genes, are regulated by colony size. Modeling results and empirical observations demonstrate that colonies less than 100 µm in diameter are too small to maximize endogenous Stat3 activation and that colonies separated by more than 400 µm can be considered independent from each other. These results define parameter boundaries for the use of ESCs in screening studies, demonstrate the importance of context in stem cell responsiveness to exogenous cues, and suggest that niche size is an important parameter in stem cell fate control

Methodological considerations concerning the development of oral dental erosion indexes: literature survey, validity and reliability

Within the context of preventing non-communicable diseases, the World Health Report (2002) and the WHO Global Oral Health Program (2003) put forward a new strategy of disease prevention and health promotion. Greater emphasis is placed on developing global policies in oral health promotion and oral disease prevention. The Decayed, Missing, Filled Teeth (DMFT) index does not meet new challenges in the field of oral health. Dental erosion seems to be a growing problem, and in some countries, an increase in erosion of teeth is associated with an increase in the consumption of beverages containing acids. Therefore, within a revision of the WHO Oral Health Surveys Basic Methods, new oral disease patterns, e.g. dental erosion, have to be taken into account. Within the last 20 years, many studies on dental erosion have been carried out and published. There has been a rapid growth in the number of indexes quantifying dental erosion process in different age groups. However, these indexes are not comparable. This article discusses quality criteria which an index intended for assessing tooth erosion should possess

Reduced Serotonin Reuptake Transporter (SERT) Function Causes Insulin Resistance and Hepatic Steatosis Independent of Food Intake

Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes