Decreasing Hospital Observation Time for Febrile Infants.

BACKGROUND: Febrile infants aged 0 to 60 days are often hospitalized for a 36-to-48 hour observation period to rule out invasive bacterial infections (IBI). Evidence suggests that monitoring blood and cerebrospinal fluid (CSF) cultures for 24 hours may be appropriate for most infants. We aimed to decrease the average culture observation time (COT) from 38 to 30 hours among hospitalized infants 0 to 60 days old over 12 months. METHODS: This quality improvement initiative occurred at a large children's hospital, in conjunction with development of a multidisciplinary evidence-based guideline for the management of febrile infants. We included infants aged 0 to 60 days admitted with fever without a clear infectious source. We excluded infants who had positive blood, urine, or CSF cultures within 24 hours of incubation and infants who were hospitalized for other indications (eg, bronchiolitis). Interventions included guideline dissemination, education regarding laboratory monitoring practices, standardized order sets, and near-time identification of failures. Our primary outcome was COT, defined as time between initiation of culture incubation and hospital discharge in hours. Interventions were tracked on an annotated statistical process control chart. Our balancing measure was identification of IBI after hospital discharge. RESULTS: In our cohort of 184 infants aged 0 to 60 days, average COT decreased from 38 hours to 32 hours after structured guideline dissemination and order-set standardization; this decrease was sustained over 17 months. IBI was not identified in any patients after discharge. CONCLUSIONS: Implementation of an evidence-based guideline through education, transparency of laboratory procedures, creation of standardized order sets, and near-time feedback was associated with shorter COT for febrile infants aged 0 to 60 days.

Association of sexually-transmitted infection and African-American race with Streptococcus agalactiae colonization in pregnancy.

BACKGROUND: Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women. METHODS: A retrospective cohort study was performed at Louisiana State University Health Sciences Center - Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010. RESULTS: Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African-American race (AOR = 2.142; 95% CI = 2.092-3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035-1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African-American race (AOR = 2.13; 95% CI = 1.20-3.78) and younger age (AOR = 0.94; 95% CI = 0.91-0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78-10.41). CONCLUSIONS: This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

Cyclohexylamine inexplicably induces antennae loss in Formosan subterranean termites (Coptotermes formosanus Shiraki): cyclohexylamine hydrogen phosphate salts are novel termiticides.

BACKGROUND: In experiments with Formosan subterranean termites (Coptotermes formosanus Shirakii), myo-inositol-2-monophosphate as the dicyclohexylammonium salt was tested among other sugar derivatives, and was found to be toxic to C. formosanus when added to a moistened filter paper food source in plastic Petri dishes. RESULTS: Curiously, over a nine-day period, the moniliform (beaded) antenna of C. formosanus deteriorated in a stepwise fashion with the most distal pseudosegment (bead) turning brown and falling off, followed by the penultimate pseudosegment, sequentially, until 7-9 days when only a stub of the antenna remained. Termites became increasingly moribund with the loss of antennae, and quit normal behavior including consuming cellulose food, and died. sn-Glycerol-3-phosphate as the dicyclohexylammonium salt also gave the same results. Dicyclohexylammonium hydrogen phosphate and monocyclohexylammonium dihydrogen phosphate were synthesized, to find a low-cost form for application to baits, both of which also showed similar toxicity. In a trial with Fibonacci series dilutions of neat cyclohexylamine, the antenna-affecting activity became apparent in the LD30 (14 days) to LD70 range of concentrations. At the higher concentrations, darkening of the most distal parts of leg extremities was noticed. CONCLUSION: Cyclohexylamine appears to be a novel termiticide with a previously unreported mechanism of toxicity. Its hydrogen phosphate salts retain the toxic effect and are inexpensive and easily synthesized. © 2017 Society of Chemical Industry.

A novel MeCP2 acetylation site regulates interaction with ATRX and HDAC1.

Methyl-CpG-binding protein-2 (MeCP2) regulates gene expression by recruiting SWI/SNF DNA helicase/ATPase (ATRX) and Histone Deacetylase-1 (HDAC1) to methylated gene regions and modulates heterochromatin association by interacting with Heterochromatin protein-1. As MeCP2 contributes to tumor suppressor gene silencing and its mutation causes Rett Syndrome, we investigated how novel post-translational-modification contributes to its function. Herein we report that upon pharmacological inhibition of SIRT1 in RKO colon and MCF-7 breast cancer cells, endogenous MeCP2 is acetylated at sites critical for binding to DNA and transcriptional regulators. We created an acetylation mimetic mutation in MeCP2 and found it to possess decreased binding to ATRX and HDAC1. Conditions inducing MeCP2 acetylation do not alter its promoter occupancy at a subset of target genes analyzed, but do cause decreased binding to ATRX and HDAC1. We also report here that a specific inhibitor of SIRT1, IV, can be used to selectively decrease H3K27me3 repressive marks on a subset of repressed target gene promoters analyzed. Lastly, we show that RKO cells over-expressing MeCP2 mutant show reduced proliferation compared to those over-expressing MeCP2-wildtype. Our study demonstrates the importance of acetylated lysine residues and suggests their key role in regulating MeCP2 function and its ability to bind transcriptional regulators.

SIRT1 regulates Dishevelled proteins and promotes transient and constitutive Wnt signaling.

Sirtuin 1 (SIRT1) is a class III histone deacetylase that deacetylates histone and nonhistone proteins to regulate gene transcription and protein function. Because SIRT1 regulates very diverse responses such as apoptosis, insulin sensitivity, autophagy, differentiation, and stem cell pluripotency, it has been a challenge to reconcile how it orchestrates such pleiotropic effects. Here we show that SIRT1 serves as an important regulator of Wnt signaling. We demonstrate that SIRT1 loss of function leads to a significant decrease in the levels of all three Dishevelled (Dvl) proteins. Furthermore, we demonstrate that SIRT1 and Dvl proteins complex in vivo and that inhibition of SIRT1 leads to changes in gene expression of Wnt target genes. Finally, we demonstrate that Wnt-stimulated cell migration is inhibited by a SIRT1 inhibitor. Because the three mammalian Dvl proteins serve as key messengers for as many as 19 Wnt ligands, SIRT1-mediated regulation of Dvl proteins may explain the diverse physiological responses observed in different cellular contexts. Previously, SIRT1 had only been shown to mediate the epigenetic silencing of Wnt antagonists. In contrast, here we report that SIRT1 regulates Dvl protein levels and Wnt signaling in several cellular contexts. These findings demonstrate that SIRT1 is a regulator of transient and constitutive Wnt signaling.