bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA
Authors: Volinia Stefano , Galasso Marco , Sana Maria Elena , Wise Timothy F. , Palatini Jeff , Huebner Kay , Croce Carlo M.
Published: February 2012

The transition from ductal carcinoma in situ to invasive ductal carcinoma is a key event in breast cancer progression that is still not well understood. To discover the microRNAs regulating this critical transition, we used 80 biopsies from invasive ductal carcinoma, 8 from ductal carcinoma in situ, and 6 from normal breast. We selected them from a recently published deep-sequencing dataset [Farazi TA, et al. (2011)Cancer Res71:4443–4453]. The microRNA profile established for the normal breast to ductal carcinoma in situ transition was largely maintained in the in situ to invasive ductal carcinoma transition. Nevertheless, a nine-microRNA signature was identified that differentiated invasive from in situ carcinoma. Specifically, let-7d, miR-210, and -221 were down-regulated in the in situ and up-regulated in the invasive transition, thus featuring an expression reversal along the cancer progression path. Additionally, we identified microRNAs for overall survival and time to metastasis. Five noncoding genes were associated with both prognostic signatures—miR-210, -21, -106b*, -197, and let-7i, with miR-210 the only one also involved in the invasive transition. To pinpoint critical cellular functions affected in the invasive transition, we identified the protein coding genes with inversely related profiles to miR-210: BRCA1, FANCD, FANCF, PARP1, E-cadherin, and Rb1 were all activated in the in situ and down-regulated in the invasive carcinoma. Additionally, we detected differential splicing isoforms with special features, including a truncated EGFR lacking the kinase domain and overexpressed only in ductal carcinoma in situ.
Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ
Authors: Wei Wei , Dutchak Paul A. , Wang Xunde , Ding Xunshan , Wang Xueqian , Bookout Angie L. , Goetz Regina , Mohammadi Moosa , Gerard Robert D. , Dechow Paul C. , Mangelsdorf David J. , Kliewer Steven A. , Wan Yihong
Published: February 2012

The endocrine hormone fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism and a promising drug for type 2 diabetes. Here we identify FGF21 as a potent regulator of skeletal homeostasis. Both genetic and pharmacologic FGF21 gain of function lead to a striking decrease in bone mass. In contrast, FGF21 loss of function leads to a reciprocal high-bone-mass phenotype. Mechanistically, FGF21 inhibits osteoblastogenesis and stimulates adipogenesis from bone marrow mesenchymal stem cells by potentiating the activity of peroxisome proliferator-activated receptor γ (PPAR-γ). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-γ agonist rosiglitazone. Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration.
An Evaluation of Redd Counts as a Measure of Bull Trout Population Size and Trend
Authors: Howell Philip J. , Sankovich Paul M.
Published: February 2012

The use of redd counts to monitor abundance and trend of bull trout Salvelinus confluentus has been clouded by uncertainties concerning measurement error, life history variation, and correspondence of redd counts to adult population size. We compared census redd counts with population estimates of mature females for a migratory fluvial population of bull trout (primarily ≥ 300 mm fork length) and for a population of small (<200 mm), likely resident, bull trout. We also compared the measurement error of the experienced surveyors who conducted the redd counts to that of a group of inexperienced surveyors. Although the regression of redd counts on adult females for the migratory population was statistically significant, a large proportion of the variation in the relationship was unexplained (r  2 = 0.47). Despite that variation, redd counts accurately reflected a greater than 50% decline in the population over 10 years; however, 5-year trends in redd counts could be misleading. Power analysis parameterized by using the variation in the number of females per redd and measurement error of experienced surveyors indicated that minimum declines of 44–56% or increases of 78–118% over 10–15 years would be necessary for detection using traditional statistical criteria. Geometric mean abundance of migratory adults derived from redd counts and adults-per-redd values from the present study and published averages were similar to measured adult numbers in most cases. For both migratory and resident populations, redd counts by experienced surveyors were substantially more accurate and precise than those by inexperienced surveyors. Counts of migratory bull trout redds were more accurate and precise than counts of resident bull trout redds, which were significantly smaller and consistently underestimated. Thus, bull trout redd counts can be used to estimate abundance levels and to detect substantial longer-term changes in abundance, particularly for migratory populations. However, the reliability of the counts depends on the skill of the surveyors.

Received April 4, 2011; accepted August 8, 2011
Feeding Rate and Frequency Affect Growth of Juvenile Atlantic Spadefish
Authors: Trushenski Jesse , Rombenso Artur , Schwarz Michael H , Bowzer John , Gause Brian , Delbos Brendan , Sampaio Luis A
Published: February 2012

The Atlantic spadefish Chaetodipterus faber is an excellent candidate for aquaculture development, but success will depend on the identification of proper feeds and feeding regimens for this species. Accordingly, we evaluated the growth performance of juvenile Atlantic spadefish (3.60 ± 0.03 g [mean ± SE]) fed at rates of 3, 5, or 7% of body weight (BW) per day, either in a single feeding (1×) or in three equal feedings (3×). Weight gain, specific growth rate, feed conversion ratio, and feed intake were significantly affected by both feeding rate and frequency. Weight gain and the specific growth rate increased significantly with feeding rate, and growth was generally greater and more efficient in the 3× groups than in the 1× groups. Fish fed at higher feeding rates accumulated significantly more lipid within the body and had associated decreases in moisture, protein, and ash content, but carcass composition was unaffected by feeding frequency. We suggest that the growth of juvenile Atlantic spadefish can be optimized when they are fed at 5–7% BW/d in three daily feedings, with 7% BW/d yielding the greatest, albeit slightly less efficient, growth.
Eye movements reveal rapid concurrent access to factual and counterfactual interpretations of the world
Authors: Ferguson Heather J.
Published: February 2012

Imagining a counterfactual world using conditionals (e.g., If Joanne had remembered her umbrella …) is common in everyday language. However, such utterances are likely to involve fairly complex reasoning processes to represent both the explicit hypothetical conjecture and its implied factual meaning. Online research into these mechanisms has so far been limited. The present paper describes two eye movement studies that investigated the time-course with which comprehenders can set up and access factual inferences based on a realistic counterfactual context. Adult participants were eye-tracked while they read short narratives, in which a context sentence set up a counterfactual world ( If … then …), and a subsequent critical sentence described an event that was either consistent or inconsistent with the implied factual world. A factual consistent condition ( Because … then …) was included as a baseline of normal contextual integration. Results showed that within a counterfactual scenario, readers quickly inferred the implied factual meaning of the discourse. However, initial processing of the critical word led to clear, but distinct, anomaly detection responses for both contextually inconsistent and consistent conditions. These results provide evidence that readers can rapidly make a factual inference from a preceding counterfactual context, despite maintaining access to both counterfactual and factual interpretations of events.
Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity
Authors: Gehrig Stefanie , Eberle Mariel-Esther , Botschen Flavia , Rimbach Katharina , Eberle Florian , Eigenbrod Tatjana , Kaiser Steffen , Holmes Walter M. , Erdmann Volker A. , Sprinzl Mathias , Bec Guillaume , Keith Gérard , Dalpke Alexander H. , Helm Mark
Published: February 2012

Naturally occurring nucleotide modifications within RNA have been proposed to be structural determinants for innate immune recognition. We tested this hypothesis in the context of native nonself-RNAs. Isolated, fully modified native bacterial transfer RNAs (tRNAs) induced significant secretion of IFN-α from human peripheral blood mononuclear cells in a manner dependent on TLR7 and plasmacytoid dendritic cells. As a notable exception, tRNATyr from Escherichia coli was not immunostimulatory, as were all tested eukaryotic tRNAs. However, the unmodified, 5′-unphosphorylated in vitro transcript of tRNATyr induced IFN-α, thus revealing posttranscriptional modifications as a factor suppressing immunostimulation. Using a molecular surgery approach based on catalytic DNA, a panel of tRNATyr variants featuring differential modification patterns was examined. Out of seven modifications present in this tRNA, 2′-O-methylated Gm18 was identified as necessary and sufficient to suppress immunostimulation. Transplantation of this modification into the scaffold of yeast tRNAPhe also resulted in blocked immunostimulation. Moreover, an RNA preparation of an E. coli trmH mutant that lacks Gm18 2′-O-methyltransferase activity was significantly more stimulatory than the wild-type sample. The experiments identify the single methyl group on the 2′-oxygen of Gm18 as a natural modification in native tRNA that, beyond its primary structural role, has acquired a secondary function as an antagonist of TLR7.
The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition
Authors: Jöckel Stefanie , Nees Gernot , Sommer Romy , Zhao Yang , Cherkasov Dmitry , Hori Hiroyuki , Ehm Gundi , Schnare Markus , Nain Marianne , Kaufmann Andreas , Bauer Stefan
Published: February 2012

Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7-deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN-α because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2′-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-α inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-α induction of influenza A virus–infected PBMCs.
Self-reactive human CD4 T cell clones form unusual immunological synapses
Authors: Schubert David A. , Gordo Susana , Sabatino Joseph J. , Vardhana Santosh , Gagnon Etienne , Sethi Dhruv K. , Seth Nilufer P. , Choudhuri Kaushik , Reijonen Helena , Nepom Gerald T. , Evavold Brian D. , Dustin Michael L. , Wucherpfennig Kai W.
Published: February 2012

Recognition of self–peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR–pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease.
Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5
Authors: Buxadé Maria , Lunazzi Giulia , Minguillón Jordi , Iborra Salvador , Berga-Bolaños Rosa , del Val Margarita , Aramburu José , López-Rodríguez Cristina
Published: February 2012

Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression of multiple TLR-induced genes in macrophages independently of osmotic stress. NFAT5 was essential for the induction of the key antimicrobial gene Nos2 (inducible nitric oxide synthase [iNOS]) in response to low and high doses of TLR agonists but is required for Tnf and Il6 mainly under mild stimulatory conditions, indicating that NFAT5 could regulate specific gene patterns depending on pathogen burden intensity. NFAT5 exhibited two modes of association with target genes, as it was constitutively bound to Tnf and other genes regardless of TLR stimulation, whereas its recruitment to Nos2 or Il6 required TLR activation. Further analysis revealed that TLR-induced recruitment of NFAT5 to Nos2 was dependent on inhibitor of κB kinase (IKK) β activity and de novo protein synthesis, and was sensitive to histone deacetylases. In vivo, NFAT5 was necessary for effective immunity against Leishmania major, a parasite whose clearance requires TLRs and iNOS expression in macrophages. These findings identify NFAT5 as a novel regulator of mammalian anti-pathogen responses.
Nosocomial Influenza in a Pediatric Hospital: Comparison of Rates of Seasonal and Pandemic 2009 Influenza A/H1N1 Infection
Authors: Ostovar Gholamabbas Amin , Kohn Nina , Yu Karl O. A. , Nullet Susan , Rubin Lorry G.
Published: February 2012

The rates of nosocomial seasonal (January 2008 to March 2009) and 2009 A/H1N1 (April 2009 to December 2010) influenza infections in a children's hospital were compared. Droplet precautions were used. The rates were similar during both periods, suggesting that use of droplet precautions did not result in a higher rate of influenza A/H1N1 infection.

Infect Control Hosp Epidemiol 2012;33(3):292-294
Prevalence of Healthcare-Associated Infections in Acute Care Hospitals in Jacksonville, Florida
Authors: Magill Shelley S. , Hellinger Walter , Cohen Jessica , Kay Robyn , Bailey Christine , Boland Bonnie , Carey Darlene , Guzman Jessica de , Dominguez Karen , Edwards Jonathan , Goraczewski Lori , Horan Teresa , Miller Melodee , Phelps Marti , Saltford Rebecca , Seibert Jacquelyn , Smith Brenda , Starling Patricia , Viergutz Bonnie , Walsh Karla , Rathore Mobeen , Guzman Nilmarie , Fridkin Scott
Published: February 2012

Objective.

To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey.

Design.

Point prevalence survey.

Patients.

Acute care inpatients of any age.

Methods.

HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection.

Results.

Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%–7.7%). Surgical site infections (n = 18), urinary tract infections (n = 9), pneumonia (n = 9), and bloodstream infections (n = 8) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs.

Conclusions.

HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Prevention's Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale.

Infect Control Hosp Epidemiol 2012;33(3):283-291
Economic Impact of Ventilator-Associated Pneumonia in a Large Matched Cohort
Authors: Kollef Marin H. , Hamilton Cindy W. , Ernst Frank R.
Published: February 2012

Objective.

To evaluate the economic impact of ventilator-associated pneumonia (VAP) on length of stay and hospital costs.

Design.

Retrospective matched cohort study.

Setting.

Premier database of hospitals in the United States.

Patients.

Eligible patients were admitted to intensive care units (ICUs), received mechanical ventilation for ≥2 calendar-days, and were discharged between October 1, 2008, and December 31, 2009.

Methods.

VAP was defined by International Classification of Diseases, Ninth Revision (ICD-9), code 997.31 and ventilation charges for ≥2 calendar-days. We matched patients with VAP to patients without VAP by propensity score on the basis of demographics, administrative data, and severity of illness. Cost was based on provider perspective and procedural cost accounting methods.

Results.

Of 88,689 eligible patients, 2,238 (2.5%) had VAP; the incidence rate was 1.27 per 1,000 ventilation-days. In the matched cohort, patients with VAP (n = 2,144) had longer mean durations of mechanical ventilation (21.8 vs 10.3 days), ICU stay (20.5 vs 11.6 days), and hospitalization (32.6 vs 19.5 days; all P< .0001) than patients without VAP (n = 2,144). Mean hospitalization costs were $99,598 for patients with VAP and $59,770 for patients without VAP (P< .0001), resulting in an absolute difference of $39,828. Patients with VAP had a lower in-hospital mortality rate than patients without VAP (482/2,144 [22.5%] vs 630/2,144 [29.4%]; P<.0001).

Conclusions.

Our findings suggest that VAP continues to occur as defined by the new specific ICD-9 code and is associated with a statistically significant resource utilization burden, which underscores the need for cost-effective interventions to minimize the occurrence of this complication.

Infect Control Hosp Epidemiol 2012;33(3):250-256
The Cross-Transmission of 2009 Pandemic Influenza A (H1N1) Infections among Healthcare Workers and Inpatients in a Chinese Tertiary Hospital
Authors: Du Mingmei , Suo Jijiang , Jia Na , Xing Yubin , Xie Lijun , Liu Yunxi
Published: February 2012

We reported 2009 H1N1 influenza infections among healthcare workers (HCWs) and inpatients and the prevention measures instituted in a large Chinese hospital. In total, 171 HCWs and 89 inpatients tested positive for H1N1. Sixteen HCWs had known hospital exposure, among whom only 7 had working-contact exposure. There was no influenza outbreak.

Infect Control Hosp Epidemiol 2012;33(3):295-298
Support for Seasonal Influenza Vaccination Requirements among US Healthcare Personnel
Authors: Maurer Jürgen , Harris Katharine M. , Black Carla L. , Euler Gary L.
Published: February 2012

Objective.

To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements.

Design.

Between lune 1 and June 30, 2010, we surveyed a sample of US HCP (n= 1,664) recruited using an existing probability-based online research panel of participants representing the US general population as a sampling frame.

Setting.

General community.

Participants.

Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings.

Methods.

We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models.

Results.

A total of 57.4% (95% confidence interval, 53.3%–61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective.

Conclusions.

A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements.

Infect Control Hosp Epidemiol2012;33(3):213-221
A randomized double‐blind crossover trial of triventricular versus biventricular pacing in heart failure
Authors: Rogers Dominic P.S. , Lambiase Pier D. , Lowe Martin D. , Chow Anthony W.C.
Published: February 2012

Aims

A significant proportion of patients implanted with biventricular (BiV) devices fail to respond. Clinical response may be improved by additional ventricular stimulation sites. This single‐centre, double‐blinded randomized crossover trial aimed to determine whether long‐term multisite ventricular pacing is superior to conventional BiV pacing in heart failure patients.

Methods and results

A total of 43 patients referred for cardiac resynchronization therapy (CRT) underwent transvenous implantation of a triventricular (TriV) device. Pacing leads were positioned in the right ventricular (RV) apex and a lateral coronary sinus (CS) branch, with a third ventricular lead implanted in a further lateral CS branch in 23 patients (group A) and on the high RV septum in 20 patients (group B). Devices were programmed in a randomized order to four pre‐determined pacing configurations: conventional BiV, TriV, and dual‐site and single‐site left bentricular (LV) or RV pacing for 3‐month periods with clinical and echo assessment at the end of each period. The primary endpoint was the comparison of 6 min walk distance (6MW) after 3 months of BiV vs. TriV pacing; secondary endpoints were Minnesota Living With Heart Failure (MLWHF) scores, and LV dimensions and function. The 12‐month follow‐up period was completed by 37 patients. Compared with BiV pacing, TriV pacing resulted in significant improvements in 6MW (451 ± 112 m vs. 425 ± 119 m, P = 0.008), MLWHF (32 ± 19 vs. 38 ± 24, P = 0.036), LV end‐systolic volume (158 ± 79mL vs. 168 ± 76 mL, P < 0.05), and ejection fraction (30 ± 8% vs. 27 ± 8%, P < 0.05).

Conclusions

TriV pacing was associated with significant improvements in clinical and echocardiographic parameters compared with BiV pacing.
Integrated risk analysis for rare marine species impacted by fishing: sustainability assessment and population trend modelling
Authors: Zhou Shijie , Milton David A. , Fry Gary C.
Published: February 2012

Zhou, S., Milton, D. A., and Fry, G. C. 2012. Integrated risk analysis for rare marine species impacted by fishing: sustainability assessment and population trend modelling. – ICES Journal of Marine Science, 69: 271–280. Risk assessment and conservation management of rare species are challenging due to a lack of data. We developed an integrated risk assessment approach to assess human impact on population sustainability of rare species. The approach involved two components: a quantitative sustainability assessment coupled with modelling trends in relative abundance. Both components took nil catches into account through zero-inflated statistical distributions that simultaneously modelled the zero and non-zero catches separately in submodels. The sustainability assessment used detection–non-detection data for population estimation and linked sustainability to easily collected life-history traits. This component provides an assessment of population sustainability at one point in time. The trend modelling applied zero-inflated negative binomial models to temporal trends in density and dispersion of species. It provided a complement to the static sustainability assessment. We applied this integrated approach to assess the risk to 14 species of rare, protected sea snakes incidentally caught in the Australian Northern Prawn Fishery. This approach can be applicable for risk assessment of many species with limited abundance data, a large number of absences and some presence–absence information only.
Drug Allergy
Authors: Smith Helen E.
Published: February 2012

Adverse drug reactions are a major cause of morbidity, complicating over 5% of therapeutic drug courses. The majority of these events are due to common predictable mechanisms linked to the way the drug works, but about 5% of all reactions are immune-mediated and constitute true allergy. Drug allergy is one of the potential causes of anaphylaxis, angioedema and urticaria and should always be considered when a patient presents with one of these conditions.
Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel
Authors: Marsakova Lenka , Touska Filip , Krusek Jan , Vlachova Viktorie
Published: February 2012

Background

The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1.

Methods

The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C.

Results

The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane.

Conclusions

The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.
Accuracy of Pain Recall in Children
Authors: Chogle Ashish , Sztainberg Marcelo , Bass Lee , Youssef Nader N. , Miranda Adrian , Nurko Samuel , Hyman Paul , Cocjin Jose , Di Lorenzo Carlo , Saps Miguel
Published: February 2012

Background and Aim:

Chronic abdominal pain (AP) is common in children. Recall of symptoms is used clinically to determine management, to assess treatment progress, and in drug studies to assess outcomes. Limited data exist on accuracy of AP recall in children. The aim of the present study was to assess ability to accurately recall AP in children.

Methods:

The study was a secondary analysis of data obtained from a double‐blind, randomized, placebo‐controlled trial, evaluating amitriptyline in children with functional gastrointestinal disorders. Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers. Those with evidence of organic disease were excluded. Patients maintained AP diary daily for 1 month (presence, frequency, and intensity). At the end of the study, patients reported the number of days of AP during previous month. Agreement between daily pain reports and recalled pain was assessed. Univariate analysis was conducted with Spearman rank correlations.

Results:

We recruited 63 children (45 girls, mean age 12.8 years). Sixteen percent children had perfect agreement on number of days of AP. Fifty‐four percent of children recalled fewer episodes of pain. The average number of days with AP by recall was 17.7/month, whereas by diary it was 23.5/month (P = 0.001). Correlation between patient recall of the last week of symptoms (r = 0.47) was no better than correlation between recall of the last 30 days of symptoms (r = 0.48). On comparing AP recall versus various pain intensities, reported AP did not reflect only AP of greater severity. Higher correlation of recall of symptoms was seen in children 11 years or younger (r = 0.59) as compared with children older than 11 years (r = 0.26).

Conclusions:

Few children can accurately recall the episodes of AP. Children commonly recall a lower frequency of AP than that assessed by prospective diary reports. Reported recall does not reflect a shorter recollection period. Recall is not related to intensity of pain. Adolescents have worse recall of symptoms.
Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis
Authors: Kong Heidi H. , Oh Julia , Deming Clay , Conlan Sean , Grice Elizabeth A. , Beatson Melony A. , Nomicos Effie , Polley Eric C. , Komarow Hirsh D. ,   NISC Comparative Sequence Program, Murray Patrick R. , Turner Maria L. , Segre Julia A.
Published: February 2012

Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
SCARECROW Has a SHORT-ROOT-Independent Role in Modulating the Sugar Response
Authors: Cui Hongchang , Hao Yueling , Kong Danyu
Published: February 2012

Sugar is essential for all cellular activities, but at high levels it inhibits growth and development. How plants balance the tradeoffs between the need for sugars and their growth inhibitory effects is poorly understood. SHORT-ROOT (SHR) and SCARECROW (SCR) are key regulators of stem cell renewal and radial patterning in the root of Arabidopsis (Arabidopsis thaliana). Recently, we identified direct targets of SHR at the genome scale. Intriguingly, among the top-ranked list, we found a number of genes that are involved in stress responses. By chromatin immunoprecipitation-polymerase chain reaction (PCR), we showed that SHR and SCR regulate a similar but not identical set of stress response genes. Consistent with this, scr and shr were found to be hypersensitive to abscisic acid (ABA). We further showed that both mutants were hypersensitive to high levels of glucose (Glc) but responded normally to high salinity and osmoticum. The endogenous levels of sucrose, Glc, and fructose were also elevated in shr and scr. Intriguingly, although shr had sugar content and developmental defects similar to those of scr, it was much less sensitive to Glc. Chromatin immunoprecipitation-PCR and reverse transcription-PCR assays as well as transgenic studies with an ABA-INSENSITIVE2 (ABI4)-β-glucuronidase reporter construct revealed that in root, SCR, but not SHR, repressed ABI4 and ABI5 directly and specifically in the apical meristem. When combined with abi4, scr became much more tolerant of high Glc. Finally, transgenic plants expressing ABI4 under the control of the SCR promoter manifested a short-root phenotype. These results together suggest that SCR has a SHR-independent role in mitigating the sugar response and that this role of SCR is important for root growth.
Potential association of Helicobacter cinaedi with atrial arrhythmias and atherosclerosis
Authors: Khan Shahzada , Okamoto Tatsuya , Enomoto Koji , Sakashita Naomi , Oyama Kohta , Fujii Shigemoto , Sawa Tomohiro , Takeya Motohiro , Ogawa Hisao , Yamabe Hiroshige , Akaike Takaaki
Published: February 2012

Helicobacter cinaedi has been increasingly recognized as an emerging pathogen. Reports of recurrent bacteremia and isolation of H. cinaedi organisms from a patient with myopericarditis led us to postulate that H. cinaedi is associated with chronic inflammatory cardiovascular diseases such as atrial arrhythmias and atherosclerosis. To assess any association of H. cinaedi with atrial arrhythmias, a retrospective case‐control study of patients attending Kumamoto University Hospital from 2005 to 2009 was performed. The arrhythmia status of these patients was determined from their electrocardiography and electrophysiological studies. Multiple logistic regression analysis was used to identify independent risk factors. In a comparison of case patients (n= 132) with control subjects (n= 137), H. cinaedi seropositivity was identified as an independent risk factor for atrial arrhythmia (odds ratio, 5.13; 95% confidence interval, 3.0–8.7; P < 0.001). There were no significant differences, however, between these two groups with respect to anti‐H. pylori IgG concentrations, anti‐Chlamydophila pneumoniae IgG concentrations, and other studied variables. IgG concentrations against H. cinaedi and H. pylori were inversely correlated, which suggests cross‐immunity between these two bacteria. Also, to explore any association of H. cinaedi with atherosclerosis, immunohistochemical analysis of atherosclerotic aortic tissues collected post mortem from nine patients was performed. Immunohistochemistry of atherosclerotic aortic tissues from all nine patients detected H. cinaedi antigens inside CD68+ macrophages. These findings provide the first evidence, to our knowledge, of a possible association of H. cinaedi with atrial arrhythmias and atherosclerosis.
A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years
Authors: Wickens K. , Black P. , Stanley T. V. , Mitchell E. , Barthow C. , Fitzharris P. , Purdie G. , Crane J.
Published: February 2012

Background

Using a double blind randomized placebo‐controlled trial (Australian New Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a high risk birth cohort, maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 (HN001) (6 × 109 cfu/day) halved the cumulative prevalence of eczema by age 2 years. Bifidobacterium animalis subsp lactis HN019 (HN019) (9 × 109 cfu/day) had no effect.

Objective

The aim of this study was to investigate the associations of HN001 and HN019 with allergic disease and atopic sensitization among these children at age 4 years, 2 years after stopping probiotic supplementation.

Methods

The presence (UK Working Party's Diagnostic Criteria) and severity SCORing Atopic Dermatitis (SCORAD) of eczema and atopy (skin prick tests) and parent‐reported symptoms of asthma and rhinoconjunctivitis were assessed using standard protocols and questions.

Results

Four‐hundred and seventy‐four infants were eligible at birth of whom 425 (90%) participated in this follow‐up. The cumulative prevalence of eczema by 4 years (Hazard ratio (HR) 0.57 (95% CI 0.39–0.83)) and prevalence of rhinoconjunctivitis at 4 years (Relative risk 0.38 (95% CI 0.18–0.83)) were significantly reduced in the children taking HN001; there were also nonsignificant reductions in the cumulative prevalence of SCORAD ≥ 10 (HR 0.74 (95% CI 0.52–1.05), wheeze (HR 0.79 (95% CI 0.59–1.07)) and atopic sensitization (HR = 0.72 (95% CI 0.48–1.06)). HN019 did not affect the prevalence of any outcome.

Conclusions and Clinical Relevance

This study showed that the protective effect of HN001 against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants.
Non‐atopic males with adult onset asthma are at risk of persistent airflow limitation
Authors: Amelink M. , de Nijs S. B. , Berger M. , Weersink E. J. , ten Brinke A. , Sterk P. J. , Bel E. H.
Published: February 2012

Background

Patients with asthma have on average a more rapid decline in FEV
1 as compared with the general population. Recent cluster analysis has revealed different asthma phenotypes that can be distinguished by age of onset and reversibility of airflow limitation.

Objective

This study aimed at detecting risk factors associated with persistent airflow limitation in patients with the adult onset asthma phenotype.

Methods

We recruited 88 patients with adult onset (≥ 18 years) asthma from an academic pulmonary outpatient clinic in the Netherlands. The associations of age, age of asthma onset, asthma duration, gender, race, atopy, smoking packyears, BMI, use of oral corticosteroids with post‐bronchodilator FEV
1/FVC were investigated.

Results

Multiple linear regression analysis showed an association of absence of atopy (r = −0.27, B = −0.26, P = 0.01) and male gender (r = 0.31, B = 0.30, P = 0.004) with post‐bronchodilator FEV
1/FVC. Multiple logistic regression analysis showed that male patients were 10.8 (CI: 2.6–45.2) times the odds than women to have an FEV
1/FVC < 0.7, and non‐atopic patients were 5.2 (CI: 1.3–20.3) times the odds to have an FEV
1/FVC < 0.7 than atopic patients.

Conclusions and Clinical Relevance

We conclude that in patients with adult onset asthma, male gender and absence of atopy are associated with persistent airflow limitation. This might suggest that amongst patients with adult onset asthma, non‐atopic male patients are at increased risk of accelerated decline in lung function.
Endogenous sex hormones and C‐reactive protein in healthy chinese men
Authors: Zhang Youjie , Gao Yong , Tan Aihua , Yang Xiaobo , Zhang Haiying , Zhang Shijun , Wu Chunlei , Lu Zheng , Wang Mengjie , Liao Ming , Qin Xue , Li Li , Hu Yanling , Mo Zengnan
Published: February 2012

Objective

To examine the association of endogenous sex hormones and sex hormone‐binding globulin (SHBG) with C‐reactive protein (CRP) in Chinese men.

Design and participants

The study population comprised 1989 men at baseline recruitment of a population‐based cohort in China. Participant information on risk factors was collected by a face‐to‐face interview and clinical examination. All subjects in the study were without taking any kind of medication for anti‐inflammation purpose or treatment of hypogonadism and with CRP value less than 10 mg/l. Data were analysed using linear regression analyses.

Results

Higher levels of total testosterone (TT, β = −0·114, 95%CI, −0·162 to −0·065), free testosterone (β = −0·059, 95%CI, −0·106 to −0·012) and SHBG (β = −0·116, 95%CI, −0·169 to −0·063) were statistically significantly related to lower levels of CRP, after adjustment for age, waist circumference (WC), triglycerides, high‐density lipoprotein cholesterol, fasting glucose, insulin, smoking status, hypertension, diabetes and family history of hypertension or diabetes. In the subgroup of men with body mass index ≥ 27·5 kg/m2 or with metabolic syndrome, findings for TT and SHBG were more pronounced, whereas the associations of TT with CRP were attenuated and nonstatistically significant among subjects with WC ≥ 90 cm or with insulin resistance. No associations were observed between estradiol, luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and CRP.

Conclusions

We have confirmed the association of androgens with reduced inflammation as measured by CRP in Chinese men. This is independent of conventional cardiovascular risk factors and is explained in part by markers of central obesity and insulin resistance, rather than metabolic syndrome.
The effects of exercise and diurnal variation on monocyte subsets and monocyte‐platelet aggregates
Authors: Shantsila Eduard , Tapp Luke D. , Wrigley Benjamin J. , Montoro‐Garcia Silvia , Ghattas Angie , Jaipersad Anthony , Lip Gregory Y. H.
Published: February 2012

Eur J Clin Invest 2012

Background  Monocytes are important mediators in the pathophysiology of cardiovascular disease, but only scarce data are available on biological and methodological factors affecting their levels.

Design  Three monocyte subsets, CD14++ CD16− CCR2+ (Mon1), CD14++ CD16+ CCR2+ (Mon2), CD14+ CD16+ CCR2− (Mon3), and monocyte‐platelet aggregates (MPAs) were analysed by flow cytometry. The effects of treadmill exercise were assessed on 12 healthy volunteers. Diurnal variation was evaluated in 16 healthy volunteers, and the effects of delayed blood processing were measured in 12 samples.

Results  Mon1 were increased when measured 15 min after exercise followed by a reduction at 1 h (P < 0·05 for both). MPAs were significantly reduced at 15 min and 1 h (P < 0·05 for both). There was significant diurnal variation in the numbers of Mon2, which were highest at 6 pm and lowest at 6 am. There were also significant diurnal variations in phagocytic activity of Mon1 and Mon2, which were highest at 12 pm and lowest at 12 am. Monocyte counts remained stable up to 2 h after venipuncture. MPAs were significantly increased at 2 h and increased further by 4 h after sampling.

Conclusions  Monocyte subset Mon2 and monocyte phagocytic activity undergo significant diurnal variation. A single bout of exercise causes a temporal increase in monocytes and a reduction in MPAs. Monocyte subset counts should be analysed within 2 h of blood sampling, whereas measurement of MPAs and monocyte CD14 and CD16 expression should be performed within 1 h.
How the ladybird got its spots: effects of resource limitation on the honesty of aposematic signals
Authors: Blount Jonathan D. , Rowland Hannah M. , Drijfhout Falko P. , Endler John A. , Inger Richard , Sloggett John J. , Hurst Gregory D. D. , Hodgson David J. , Speed Michael P.
Published: February 2012

1. Prey species often possess defences (e.g. toxins) coupled with warning signals (i.e. aposematism). There is growing evidence that the expression of aposematic signals often varies within species and correlates with the strength of chemical defences. This has led to the speculation that such signals may be ‘honest’, with signal reliability ensured by the costliness of producing or maintaining aposematic traits.

2. We reared larval seven‐spot ladybirds (Coccinella septempunctata) on a Low or High aphid diet and measured the effects on warning signal expression (elytral carotenoid pigmentation, conspicuousness, spot size), levels of defensive alkaloids (precoccinelline, coccinelline), and relationships between these traits.

3. High‐diet individuals had greater total precoccinelline levels, and elytra carotenoid concentrations at adulthood which was detectable to a typical avian predator. However, larval diet did not significantly affect adult body mass or size, spot size or coccinelline levels.

4. Elytra carotenoid concentrations correlated positively with total precoccinelline levels in both diet groups and sexes. However, the relationship between elytra carotenoid concentrations and total levels of coccinelline depended on sex: in both diet groups, elytra carotenoids and coccinelline levels were positively correlated in females, but negatively correlated in males. Spot size and coccinelline levels correlated positively in Low‐diet individuals, but negatively in High‐diet individuals.

5. These results point to physiological linkages between components of aposematism, which are modulated by resource (i.e. food) availability and affect the honesty of signals. Developmental diet, but also sex, influenced the relationships between signals and toxin levels. Ladybirds are sexually size dimorphic, and thus in comparison with males, females may be more susceptible to resource limitation and more likely to be honest signallers.