Age-Stratified Cut-Off Values for Serum Levels of N-Terminal ProB-Type Natriuretic Peptide and Mortality from Sepsis in Children Under Age 18 Years: A Retrospective Study from a Single Center.

BACKGROUND The N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) is an established predictive marker for sepsis-related mortality in adult. This retrospective study aimed to determine age-stratified cut-off values for serum levels of NT-proBNP and mortality from sepsis in children under 18 years. MATERIAL AND METHODS Patients were stratified by age as follows: <1 year, 1-3 years, 4-6 years, and 7-18 years (age groups). The control group consisted of age- and sex-matched healthy children. Serum NT-proBNP levels were detected by laboratory assays in the participants. The appropriate serum NT-proBNP cut-off values for predicting short-term mortality of the sepsis patients were calculated via receiver operating characteristic (ROC) curve analyses. RESULTS Among 327 pediatric patients with sepsis, the serum NT-proBNP cut-off concentrations for predicting sepsis-related mortality in the <1 year, 1-3 years, 4-6 years, and 7-18 years age groups were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively (P<0.001). The area under the ROC curve (AUC) values for these were 0.815, 0.812, 0.806 and 0.725, respectively (P<0.001). CONCLUSIONS This retrospective study provided the age range-specific serum NT-proBNP cut- off concentrations for predicting short-term mortality in children. In children <1 year, 1-3 years, 4-6 years, and 7-18 years, age-stratified cut-off values that predicted sepsis-associated mortality were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively.

Characterization of the complete mitochondrial genome of Coprinellus micaceus, a wild saprobic mushroom in China.

The Glistening Inkcap (Coprinellus micaceus) is a wild saprobic mushroom in China. In this study, we assembled and annotated its complete mitochondrial genome using raw data sequenced through Illumina NovaSeq 6000 platform (Illumina, San Diego, CA). The length of the C. micaceus mitochondrial genome is 65,450 bp with 33.05% GC content. Totally, 41 genes, including 14 protein-coding genes, 25 tRNAs and 2 rRNAs were identified in the mitochondrial genome. Phylogenetic analysis showed that the mitochondrial genome relationship between C. micaceus and Coprinopsis cinerea was the closest.

Multifaceted regulation of somatic cell reprogramming by mRNA translational control.

Translational control plays a pivotal role in the regulation of the pluripotency network in embryonic stem cells, but its effect on reprogramming somatic cells to pluripotency has not been explored. Here, we show that eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translational repressors, have a multifaceted effect on the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs). Loss of 4E-BP expression attenuates the induction of iPSCs at least in part through increased translation of p21, a known inhibitor of somatic cell reprogramming. However, MEFs lacking both p53 and 4E-BPs show greatly enhanced reprogramming resulting from a combination of reduced p21 transcription and enhanced translation of endogenous mRNAs such as Sox2 and Myc and can be reprogrammed through the expression of only exogenous Oct4. Thus, 4E-BPs exert both positive and negative effects on reprogramming, highlighting the key role that translational control plays in regulating this process.

Effect of hypothermia on doxorubicin-induced cardiac myoblast signaling and cell death.

BACKGROUND: Anthracyclines (AC) are useful chemotherapeutic agents whose principal limitation is cardiac toxicity, which may progress to heart failure, transplantation or even death. We have shown that this toxicity involves oxidative stress-induced activation of the DNA damage pathway. Hypothermia has been shown to be protective against other diseases involving oxidative stress but has not been studied in models of AC toxicity. METHODS: In the current experiments, H9C2 cardiac myoblasts were treated with varying concentrations of the AC doxorubicin (DOX) during normothermia (37°C) or mild hypothermia (35°C). Total cell death was assayed using trypan blue exclusion and apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling (TUNEL) staining. Oxidative stress was assayed using the fluorescent indicator 2'7'-dichlorofluorescein diacetate. DNA damage pathway activation was assayed by immunostaining for H2AX and p53. Mitochondrial membrane potential was assayed by JC-1 staining. RESULTS: At all concentrations of DOX examined (1, 2.5 and 5 µM), hypothermia reduced oxidative stress, activation of H2AX and p53, loss of mitochondrial membrane potential and total and apoptotic cell death (P=.001-.03 for each observation). CONCLUSIONS: The reduction of oxidative stress-induced activation of the DNA damage pathway and consequent cell death by mild hypothermia supports a possible protective role to reduce the clinical impact of DOX-induced cardiac toxicity. Such an approach may allow expanded use of these effective chemotherapeutic agents to increase cancer cure rates.

Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDS-based micronutrients.

OBJECTIVES: To investigate whether the micronutrients that were shown to reduce the risk of development of age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) can have the same effect on the development of diabetic retinopathy in rats, and to understand the possible mechanisms. METHODS: Streptozotocin-induced diabetic rats received a powdered diet with or without supplemental micronutrients (ascorbic acid, vitamin E, beta-carotene, zinc, and copper). The retina was used after the rats had diabetes for 12 months to detect vascular histopathology and to measure the biochemical parameters and messenger RNA levels of the genes involved in oxidative and nitrative stress. RESULTS: The AREDS-based micronutrients prevented a diabetes-induced increase in the number of retinal acellular capillaries. In the same rats, micronutrients inhibited increases in retinal oxidatively modified DNA and nitrotyrosine and decreases in manganese superoxide dismutase. Diabetes-induced alterations in the messenger RNA expression of mitochondrial electron transport complex III (coenzyme Q cytochrome-c reductase) and inducible nitric oxide synthase were also prevented. CONCLUSION: Age-Related Eye Disease Study-based micronutrients inhibit the development of diabetic retinopathy in rodents by inhibiting oxidative and nitrative stress. CLINICAL RELEVANCE: Micronutrients that slow down the onset and progression of age-related macular degeneration have the potential to inhibit the development of diabetic retinopathy.

Helicobacter pylori infection in the pharynx of patients with chronic pharyngitis detected with TDI-FP and modified Giemsa stain.

AIM: To detect whether there is Helicobacter pylori (H pylori) colonization in the pharynx mucous membrane of healthy people and whether chronic pharyngitis is related to H pylori infection. METHODS: Fifty cases of chronic pharyngitis refractory over three months were prospectively studied from March 2004 to August 2004 in the otolaryngology outpatient department of the Second Hospital of Xi'an Jiaotong University. Template-directed dye-terminator incorporated with fluorescence polarization detection (TDI-FP) and modified Giemsa stain were used to examine pharynx mucous membrane tissue for H pylori colonization in the patients with chronic pharyngitis and the healthy people as a control group. RESULTS: In the control group, no people were detected to have H pylori in the pharynx. In contrast, in 50 cases with chronic pharyngitis, 19 (38.0%) cases were H pylori positive with a TDI-FP assay and 4 (8%) cases were TDI-FP positive with Giemsa staining in the pharynx. Sixteen of the 50 pharyngitis cases had stomach ailment history, 11 cases (68.8%) of these 16 patients were determined to be H pylori positive in the pharynx with the TDI-FP assay. c2 test showed that this infection rate was remarkably higher (P=0.0007) than that in the cases without stomach ailment history. Giemsa staining showed that 3 cases (18.8%) of the patients with stomach ailment history were infected with H pylori in the pharynx, which was remarkably higher (P=0.042) than that in the patients without stomach ailment history (1 case, which was 2.9%). CONCLUSION: H pylori may not be detected in the pharynx of healthy people. Chronic pharyngitis may be related to H pylori infection. The infection rate with H pylori in the pharynx is higher in patients with stomach ailment histories than in patients without stomach ailment histories, suggesting that chronic pharyngitis may be related to stomach ailment history.