Validity of bag urine culture for predicting urinary tract infections in febrile infants: a paired comparison of urine collection methods.

PURPOSE: Catheter urine (CATH-U) and suprapubic aspiration (SPA) are reliable urine collection methods for confirming urinary tract infections (UTI) in infants. However, noninvasive and easily accessible collecting bag urine (CBU) is widely used, despite its high contamination rate. This study investigated the validity of CBU cultures for diagnosing UTIs, using CATH-U culture results as the gold standard. METHODS: We retrospectively analyzed 210 infants, 2- to 24-month-old, who presented to a tertiary care hospital's pediatrics department between September 2008 and August 2013. We reviewed the results of CBU and CATH-U cultures from the same infants. RESULTS: CBU results, relative to CATH-U culture results (≥10(4) colony-forming units [CFU]/mL) were widely variable, ranging from no growth to ≥10(5) CFU/mL. A CBU cutoff value of ≥10(5) CFU/mL resulted in false-positive and false-negative rates of 18% and 24%, respectively. The probability of a UTI increased when the CBU bacterial count was ≥10(5)/mL for all infants, both uncircumcised male infants and female infants (likelihood ratios [LRs], 4.16, 4.11, and 4.11, respectively). UTIs could not be excluded for female infants with a CBU bacterial density of 10(4)-10(5) (LR, 1.40). The LRs for predicting UTIs based on a positive dipstick test and a positive urinalysis were 4.19 and 3.11, respectively. CONCLUSION: The validity of obtaining urine sample from a sterile bag remains questionable. Inconclusive culture results from CBU should be confirmed with a more reliable method.

Erratum: Validity of bag urine culture for predicting urinary tract infections in febrile infants: a paired comparison of urine collection methods.

[This corrects the article on p. 183 in vol. 58, PMID: 26124849.].

Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.

BACKGROUND: Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies that have intrinsic limitations. RESULTS: We use next generation sequencing methods, RNA-seq and ChIP-seq for RNA polymerase II and several histone methylation marks, to obtain a more complete view of cocaine-induced changes in gene expression and associated adaptations in numerous modes of chromatin regulation in the mouse nucleus accumbens, a key brain reward region. We demonstrate an unexpectedly large number of pre-mRNA splicing alterations in response to repeated cocaine treatment. In addition, we identify combinations of chromatin changes, or signatures, that correlate with cocaine-dependent regulation of gene expression, including those involving pre-mRNA alternative splicing. Through bioinformatic prediction and biological validation, we identify one particular splicing factor, A2BP1(Rbfox1/Fox-1), which is enriched at genes that display certain chromatin signatures and contributes to drug-induced behavioral abnormalities. Together, this delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of regulation by which cocaine alters the brain. CONCLUSIONS: We establish combinatorial chromatin and transcriptional profiles in mouse nucleus accumbens after repeated cocaine treatment. These results serve as an important resource for the field and provide a template for the analysis of other systems to reveal new transcriptional and epigenetic mechanisms of neuronal regulation.

Essential role of poly(ADP-ribosyl)ation in cocaine action.

Many of the long-term effects of cocaine on the brain's reward circuitry have been shown to be mediated by alterations in gene expression. Several chromatin modifications, including histone acetylation and methylation, have been implicated in this regulation, but the effect of other histone modifications remains poorly understood. Poly(ADP-ribose) polymerase-1 (PARP-1), a ubiquitous and abundant nuclear protein, catalyzes the synthesis of a negatively charged polymer called poly(ADP-ribose) or PAR on histones and other substrate proteins and forms transcriptional regulatory complexes with several other chromatin proteins. Here, we identify an essential role for PARP-1 in cocaine-induced molecular, neural, and behavioral plasticity. Repeated cocaine administration, including self-administration, increased global levels of PARP-1 and its mark PAR in mouse nucleus accumbens (NAc), a key brain reward region. Using PARP-1 inhibitors and viral-mediated gene transfer, we established that PARP-1 induction in NAc mediates enhanced behavioral responses to cocaine, including increased self-administration of the drug. Using chromatin immunoprecipitation sequencing, we demonstrated a global, genome-wide enrichment of PARP-1 in NAc of cocaine-exposed mice and identified several PARP-1 target genes that could contribute to the lasting effects of cocaine. Specifically, we identified sidekick-1--important for synaptic connections during development--as a critical PARP-1 target gene involved in cocaine's behavioral effects as well as in its ability to induce dendritic spines on NAc neurons. These findings establish the involvement of PARP-1 and PARylation in the long-term actions of cocaine.

Detection of human rhinovirus C in children with acute lower respiratory tract infections in South Korea.

Recently, HRV-C was identified as a new species of HRV, but its spectrum of clinical disease is still not clear. The purpose of this study was to investigate the molecular epidemiology of HRVs in children with acute lower respiratory tract infections (LRTIs). A total of 54 HRV-positive samples that were negative for other respiratory viruses were sequenced. HRV-A was detected in 33, HRV-B in 4, and HRV-C in 17 of these samples. All HRV-C-positive patients showed favorable clinical outcomes. We confirmed the presence of HRV-C in children with LRTIs, but its association with clinical severity is not clear.

Hematuria and proteinuria in a mass school urine screening test.

A total of 1,044 school children identified with hematuria and/or proteinuria during a mass school urine screening test were referred to pediatric nephrologists at 13 hospitals in Korea. These children had isolated hematuria (IH) (60.1%), isolated proteinuria (IP) (26.4%: transient, 19.6%; orthostatic, 4.9%; persistent, 1.9%) or combined hematuria and proteinuria (CHP) (13.5%). The patient's history, physical examination, laboratory tests, kidney ultrasound and Doppler ultrasonography were obtained. Renal biopsies were performed on 113 children who showed severe proteinuria, hypertension, abnormal renal function, family history of chronic renal disease, systemic diseases or persistent hematuria and/or proteinuria for more than 12 months. IgA nephropathy (IgAN), thin basement membrane nephropathy (TBMN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), other GN, Alport syndrome and lupus nephritis were detected. IgAN and TBMN were the most common causes in the CHP group and IH group, respectively. Abnormal findings on the renal ultrasound with or without Doppler ultrasonography were noted in 147 cases (suspected nutcracker phenomenon, 65; increased parenchymal echogenicity, 40; hydronephrosis, 15). This study showed that the use of a mass school urine screening program can detect chronic renal disease in its early stage and recommends that more attention should be paid to identifying those children with CHP and massive proteinuria. A school urine screening program can detect chronic renal disease in its early stage. When mass screening is used, the initial aggressive diagnostic procedures such as renal biopsy are not needed. In addition, a regular follow-up for those children with IH and IP is certainly warranted.

Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract, BT-11.

We carried out this study to search a new active constituent that had cognitive enhancing activity and low side effects from natural source. We found that the extract of dried root of Polygala tenuifolia Willdenow (BT-11, 10 mg/kg, i.p.) could significantly reverse scopolamine-induced cognitive impairments in rat, using a passive avoidance and a water maze test. We also investigated the effects of BT-11 on neurotoxicity induced by glutamate (Glu) and toxic metabolites of amyloid precursor protein (APP) such as amyloid beta protein (A beta) and C-terminal fragment of APP (CT) in primary cultured neurons of rat. The pretreatment of BT-11 (0.5, 3, and 5 micro g/ml) significantly reduced cell death induced by Glu (1 mM), A beta (10 micro M) and CT105 (10 micro M) in a dose-dependent manner. In addition, BT-11 inhibited acetylcholinesterase (AChE) activity in a dose-dependent and non-competitive manner (IC(50) value; 263.7 micro g/ml). Our novel findings suggest the possibility that this extract may have some protective effects against neuronal death and cognitive impairments in Alzheimer's disease (AD), or other neurodegenerative diseases related to excitotoxicity and central cholinergic dysfunction.