Background The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear. Objective We sought to examine ...the prevalence of rhinovirus infections in relation to the atopic status of children treated for wheezing in Costa Rica, a country with an increased asthma burden. Methods The children enrolled (n = 287) were 7 through 12 years old. They included 96 with acute wheezing, 65 with stable asthma, and 126 nonasthmatic control subjects. PCR methods, including gene sequencing to identify rhinovirus strains, were used to identify viral pathogens in nasal washes. Results were examined in relation to wheezing, IgE, allergen-specific IgE antibody, and fraction of exhaled nitric oxide levels. Results Sixty-four percent of wheezing children compared with 13% of children with stable asthma and 13% of nonasthmatic control subjects had positive test results for rhinovirus ( P < .001 for both comparisons). Among wheezing subjects, 75% of the rhinoviruses detected were group C strains. High titers of IgE antibodies to dust mite allergen (especially Dermatophagoides species) were common and correlated significantly with total IgE and fraction of exhaled nitric oxide levels. The greatest risk for wheezing was observed among children with titers of IgE antibodies to dust mite of 17.5 IU/mL or greater who tested positive for rhinovirus (odds ratio for wheezing, 31.5; 95% CI, 8.3-108; P < .001). Conclusions High titers of IgE antibody to dust mite allergen were common and significantly increased the risk for acute wheezing provoked by rhinovirus among asthmatic children.
Isotopic ($\delta^{17}$O and $\delta^{18}$O) measurements of stratospheric and mesospheric carbon dioxide (CO$_2$) and oxygen (O$_2$), along with trace species concentrations (N$_2$O, CO, and ...CO$_2$), were made in samples collected from a rocket-borne cryogenic whole air sampler. A large mass-independent isotopic anomaly was observed in CO$_2$, which may in part derive from photochemical coupling to ozone (O$_3$). The data also require an additional isotopic fractionation process, which is presently unidentified. Mesospheric O$_2$ isotope ratios differed from those in the troposphere and stratosphere. The cause of this isotopic variation in O$_2$ is presently unknown. The inability to account for these observations represents a fundamental gap in the understanding of the O$_2$ chemistry in the stratosphere and mesosphere.
In order to assess the effect of the N-glycans associated with the GP5 neutralization epitope of porcine reproductive and respiratory syndrome virus (PRRSV) on the neutralizing antibody (Ab) response ...of swine, groups of young pigs were infected with PRRSV strains differing in N-glycosylation pattern. The humoral immune response to strain VR-2332, harboring four potential N-glycan sites, was compared to that of two natural field isolates carrying mutations either abolishing the N-glycosylation site at position 44 (N44) or the two N-glycosylation sites in the hypervariable region upstream of the neutralization epitope (HV-1). The pigs were bled at intervals and their sera were assayed for neutralizing Abs by indirect and competition ELISAs using peptides containing the GP5 neutralization epitope, and selectively for infectivity neutralization of a number of PRRSV strains. In addition, viremia was monitored by quantitative RT-PCR, and anti-N-protein Ab formation was measured by HerdChek ELISA. The neutralizing Ab responses as measured by peptide ELISA varied greatly between individual pigs infected with each PRRSV strain. Some pigs generated high titers of peptide binding Abs between 7 and 28 days post infection (p.i.), whereas other pigs had not generated a response by 90 days p.i. However, the HV-1-infected pigs generated Abs to the neutralization epitope more rapidly and to a 5-10 times higher level than VR-2332-infected pigs, and the Abs neutralized the homologous HV-1 virus 10-20 times more efficiently than PRRSV strains VR-2332, N44, MN184, or SDSU73. In contrast, most N44-infected pigs generated neutralizing Abs only after 42 days p.i. and only to low levels. The results suggest that the deletions of the N-glycans or other amino acid substitutions in the GP5 ectodomains of the mutants affect the immunogenicity of the neutralization epitope and the specificity of the Abs raised to it but not the sensitivity of the virions to Ab neutralization.
This article provides an overview of current research on flavonoids as presented during a workshop entitled, "Flavonoids and Heart Health," held by the ILSI North America Project Committee on ...Flavonoids in Washington, DC, May 31 and June 1, 2005. Because a thorough knowledge and understanding about the science of flavonoids and their effects on health will aid in establishing dietary recommendations for bioactive components such as flavonoids, a systematic review of the science of select flavonoid classes (i.e., flavonols, flavones, flavanones, isoflavones, flavan-3-ols, anthocyanins, and proanthocyanidins) was presented. The objectives of the workshop were to 1) present and discuss current research on flavonoid intake and the relation between flavonoids and heart health; 2) develop information that could lead to expert consensus on the state-of-the-science of dietary intake of flavonoids on heart health; and 3) summarize and prioritize the research needed to establish the relations between specific flavonoids and heart health. Presentations included the basics of the biology of flavonoids, including the types and distribution in foods, analytical methodologies used to determine the amounts in foods, the bioavailability, the consumption patterns and potential biomarkers of intake, risk assessment and safety evaluation, structure/function claims, and the proposed mechanism(s) of the relation between certain flavonoids and heart health endpoints. Data presented support the concept that certain flavonoids in the diet can be associated with significant health benefits, including heart health. Research gaps were identified to help advance the science.
The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of acetaminophen. An ...evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of acetaminophen alone and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care. The panel's recommendations follow. These recommendations are provided in chronological order of likely clinical use. The grade of recommendation is provided in parentheses. 1) The initial history obtained by the specialist in poison information should include the patient's age and intent (Grade B), the specific formulation and dose of acetaminophen, the ingestion pattern (single or multiple), duration of ingestion (Grade B), and concomitant medications that might have been ingested (Grade D). 2) Any patient with stated or suspected self-harm or who is the recipient of a potentially malicious administration of acetaminophen should be referred to an emergency department immediately regardless of the amount ingested. This referral should be guided by local poison center procedures (Grade D). 3) Activated charcoal can be considered if local poison center policies support its prehospital use, a toxic dose of acetaminophen has been taken, and fewer than 2 hours have elapsed since the ingestion (Grade A). Gastrointestinal decontamination could be particularly important if acetylcysteine cannot be administered within 8 hours of ingestion. Acute, single, unintentional ingestion of acetaminophen: 1) Any patient with signs consistent with acetaminophen poisoning (e.g., repeated vomiting, abdominal tenderness in the right upper quadrant or mental status changes) should be referred to an emergency department for evaluation (Grade D). 2) Patients less than 6 years of age should be referred to an emergency department if the estimated acute ingestion amount is unknown or is 200 mg/kg or more. Patients can be observed at home if the dose ingested is less than 200 mg/kg (Grade B). 3) Patients 6 years of age or older should be referred to an emergency department if they have ingested at least 10 g or 200 mg/kg (whichever is lower) or when the amount ingested is unknown (Grade D). 4) Patients referred to an emergency department should arrive in time to have a stat serum acetaminophen concentration determined at 4 hours after ingestion or as soon as possible thereafter. If the time of ingestion is unknown, the patient should be referred to an emergency department immediately (Grade D). 5) If the initial contact with the poison center occurs more than 36 hours after the ingestion and the patient is well, the patient does not require further evaluation for acetaminophen toxicity (Grade D). Repeated supratherapeutic ingestion of acetaminophen (RSTI): 1) Patients under 6 years of age should be referred to an emergency department immediately if they have ingested: a) 200 mg/kg or more over a single 24-hour period, or b) 150 mg/kg or more per 24-hour period for the preceding 48 hours, or c) 100 mg/kg or more per 24-hour period for the preceding 72 hours or longer (Grade C). 2) Patients 6 years of age or older should be referred to an emergency department if they have ingested: a) at least 10 g or 200 mg/kg (whichever is less) over a single 24-hour period, or b) at least 6 g or 150 mg/kg (whichever is less) per 24-hour period for the preceding 48 hours or longer. In patients with conditions purported to increase susceptibility to acetaminophen toxicity (alcoholism, isoniazid use, prolonged fasting), the dose of acetaminophen considered as RSTI should be greater than 4 g or 100 mg/kg (whichever is less) per day (Grade D). 3) Gastrointestinal decontamination is not needed (Grade D). Other recommendations: 1) The out-of-hospital management of extended-release acetaminophen or multi-drug combination products containing acetaminophen is the same as an ingestion of acetaminophen alone (Grade D). However, the effects of other drugs might require referral to an emergency department in accordance with the poison center's normal triage criteria. 2) The use of cimetidine as an antidote is not recommended (Grade A).
Abstract Objective We investigated the relative effects of fatigue, depressive symptoms, and hopelessness on prognosis at 2-year follow-up in percutaneous coronary intervention (PCI) patients. ...Methods Consecutively admitted PCI patients ( n =534) treated with paclitaxel-eluting stent as the default strategy completed the Maastricht Questionnaire (MQ) at baseline. Apart from an overall vital exhaustion score, the MQ also assesses fatigue (seven items; Cronbach's α =.87) and depressive symptoms (seven items; Cronbach's α =.83), with hopelessness (one item) comprised in the depressive symptom items. Patients were followed up for adverse clinical events (mortality and nonfatal myocardial infarction) at 2 years. Results At 2-year follow-up, there were 31 clinical events. In univariable analyses, overall vital exhaustion and depressive symptoms, but not fatigue, were associated with adverse prognosis; in multivariable analysis, depressive symptoms hazard ratio (HR)=2.69; 95% confidence interval (95% CI)=1.31–5.55 remained the only predictor of clinical outcome. Among the depressive symptoms, hopelessness (HR=3.44; 95% CI=1.65–7.19) was the most cardiotoxic symptom. The incidence of clinical events was higher in the high-hopelessness patients (11% vs. 3%; P =.001) than in the low-hopelessness patients. Hopelessness (HR=3.36; 95% CI=1.58–7.14; P =.002) remained an independent predictor of clinical outcome at 2 years in adjusted analysis. Conclusion Symptoms of depression, but not fatigue, predicted adverse clinical events. Hopelessness was the most cardiotoxic symptom, associated with a more than three-fold risk of clinical events 2 years post-PCI. Screening for hopelessness may lead to the identification of high-risk patients.
Doppler weather radar imaging enabled the rapid recovery of the Sutter's Mill meteorite after a rare 4-kiloton of TNT—equivalent asteroid impact over the foothills of the Sierra Nevada in northern ...California. The recovered meteorites survived a record high-speed entry of 28.6 kilometers per second from an orbit close to that of Jupiter-family comets (Tisserand's parameter = 2.8 ± 0.3). Sutter's Mill is a regolith breccia composed of CM (Mighei)—type carbonaceous chondrite and highly reduced xenolithic materials. It exhibits considerable diversity of mineralogy, petrography, and isotope and organic chemistry, resulting from a complex formation history of the parent body surface. That diversity is quickly masked by alteration once in the terrestrial environment but will need to be considered when samples returned by missions to C-class asteroids are interpreted.
Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders ...(NDDs). The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders. A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network was used including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments. Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control. Normalized mutual information was used to determine top contributing model features. Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups. Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups. Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences. Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning. Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group. Future work is needed to build on this early attempt through replication of the current findings in independent samples and testing longitudinally for prognostic value.
A review of U.S. poison center data for 2004 showed over 12,000 exposures to tricyclic antidepressants (TCAs). A guideline that determines the conditions for emergency department referral and ...prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce healthcare costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate prehospital triage and management of patients with suspected ingestions of TCAs by 1) describing the manner in which an ingestion of a TCA might be managed, 2) identifying the key decision elements in managing cases of TCA ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to ingestion of TCAs alone. Co-ingestion of additional substances could require different referral and management recommendations depending on their combined toxicities. This guideline is based on the assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) Patients with suspected self-harm or who are the victims of malicious administration of a TCA should be referred to an emergency department immediately (Grade D). 2) Patients with acute TCA ingestions who are less than 6 years of age and other patients without evidence of self-harm should have further evaluation including standard history taking and determination of the presence of co-ingestants (especially other psychopharmaceutical agents) and underlying exacerbating conditions, such as convulsions or cardiac arrhythmias. Ingestion of a TCA in combination with other drugs might warrant referral to an emergency department. The ingestion of a TCA by a patient with significant underlying cardiovascular or neurological disease should cause referral to an emergency department at a lower dose than for other individuals. Because of the potential severity of TCA poisoning, transportation by EMS, with close monitoring of clinical status and vital signs en route, should be considered (Grade D). 3) Patients who are symptomatic (e.g., weak, drowsy, dizzy, tremulous, palpitations) after a TCA ingestion should be referred to an emergency department (Grade B). 4) Ingestion of either of the following amounts (whichever is lower) would warrant consideration of referral to an emergency department: an amount that exceeds the usual maximum single therapeutic dose or an amount equal to or greater than the lowest reported toxic dose. For all TCAs except desipramine, nortriptyline, trimipramine, and protriptyline, this dose is >5 mg/kg. For despiramine it is >2.5 mg/kg; for nortriptyline it is >2.5 mg/kg; for trimipramine it is >2.5 mg/kg; and for protriptyline it is >1 mg/kg. This recommendation applies to both patients who are naïve to the specific TCA and to patients currently taking cyclic antidepressants who take extra doses, in which case the extra doses should be added to the daily dose taken and then compared to the threshold dose for referral to an emergency department (Grades B/C). 5) Do not induce emesis (Grade D). 6) The risk-to-benefit ratio of prehospital activated charcoal for gastrointestinal decontamination in TCA poisoning is unknown. Prehospital activated charcoal administration, if available, should only be carried out by health professionals and only if no contraindications are present. Do not delay transportation in order to administer activated charcoal (Grades B/D). 7) For unintentional poisonings, asymptomatic patients are unlikely to develop symptoms if the interval between the ingestion and the initial call to a poison center is greater than 6 hours. These patients do not need referral to an emergency department facility (Grade C). 8) Follow-up calls to determine the outcome for a TCA ingestions ideally should be made within 4 hours of the initial call to a poison center and then at appropriate intervals thereafter based on the clinical judgment of the poison center staff (Grade D). 9) An ECG or rhythm strip, if available, should be checked during the prehospital assessment of a TCA overdose patient. A wide-complex arrhythmia with a QRS duration longer than 100 msec is an indicator that the patient should be immediately stabilized, given sodium bicarbonate if there is a protocol for its use, and transported to an emergency department (Grade B). 10) Symptomatic patients with TCA poisoning might require prehospital interventions, such as intravenous fluids, cardiovascular agents, and respiratory support, in accordance with standard ACLS guidelines (Grade D). 11) Administration of sodium bicarbonate might be beneficial for patients with severe or life-threatening TCA toxicity if there is a prehospital protocol for its use (Grades B/D). 12) For TCA-associated convulsions, benzodiazepines are recommended (Grade D). 13) Flumazenil is not recommended for patients with TCA poisoning (Grade D).
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