Showing papers by "Saint Louis University published in 2011"

Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection

Abstract: A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log 10 IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was adminis­ tered in 41 to 46% of boceprevir­treated patients and 21% of controls. Conclusions The addition of boceprevir to peginterferon–ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon– ribavirin alone. (Funded by Scher­ ing­Plough [now Merck]; HCV RESPOND­2 ClinicalTrials.gov number, NCT00708500.)

The Prevalence, Severity, and Distribution of Childhood Food Allergy in the United States

Abstract: OBJECTIVE: The goal of this study was to better estimate the prevalence and severity of childhood food allergy in the United States. METHODS: A randomized, cross-sectional survey was administered electronically to a representative sample of US households with children from June 2009 to February 2010. Eligible participants included adults (aged 18 years or older) able to complete the survey in Spanish or English who resided in a household with at least 1 child younger than 18 years. Data were adjusted using both base and poststratification weights to account for potential biases from sampling design and nonresponse. Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy. Multiple logistic regression models were constructed to identify characteristics significantly associated with outcomes. RESULTS: Data were collected for 40 104 children; incomplete responses for 1624 children were excluded, which yielded a final sample of 38 480. Food allergy prevalence was 8.0% (95% confidence interval [CI]: 7.6–8.3). Among children with food allergy, 38.7% had a history of severe reactions, and 30.4% had multiple food allergies. Prevalence according to allergen among food-allergic children was highest for peanut (25.2% [95% CI: 23.3–27.1]), followed by milk (21.1% [95% CI: 19.4–22.8]) and shellfish (17.2% [95% CI: 15.6–18.9]). Odds of food allergy were significantly associated with race, age, income, and geographic region. Disparities in food allergy diagnosis according to race and income were observed. CONCLUSIONS: Findings suggest that the prevalence and severity of childhood food allergy is greater than previously reported. Data suggest that disparities exist in the clinical diagnosis of disease.

Friends with benefits: On the positive consequences of pet ownership.

Abstract: Social support is critical for psychological and physical well-being, reflecting the centrality of belongingness in our lives. Human interactions often provide people with considerable social support, but can pets also fulfill one’s social needs? Although there is correlational evidence that pets may help individuals facing significant life stressors, little is known about the well-being benefits of pets for everyday people. Study 1 found in a community sample that pet owners fared better on several well-being (e.g., greater self-esteem, more exercise) and individual-difference (e.g., greater conscientiousness, less fearful attachment) measures. Study 2 assessed a different community sample and found that owners enjoyed better well-being when their pets fulfilled social needs better, and the support that pets provided complemented rather than competed with human sources. Finally, Study 3 brought pet owners into the laboratory and experimentally demonstrated the ability of pets to stave off negativity caused by social rejection. In summary, pets can serve as important sources of social support, providing many positive psychological and physical benefits for their owners.

Neonatal resuscitation and immediate newborn assessment and stimulation for the prevention of neonatal deaths: a systematic review, meta-analysis and Delphi estimation of mortality effect

Abstract: Of 136 million babies born annually, around 10 million require assistance to breathe. Each year 814,000 neonatal deaths result from intrapartum-related events in term babies (previously “birth asphyxia”) and 1.03 million from complications of prematurity. No systematic assessment of mortality reduction from tactile stimulation or resuscitation has been published. To estimate the mortality effect of immediate newborn assessment and stimulation, and basic resuscitation on neonatal deaths due to term intrapartum-related events or preterm birth, for facility and home births. We conducted systematic reviews for studies reporting relevant mortality or morbidity outcomes. Evidence was assessed using GRADE criteria adapted to provide a systematic approach to mortality effect estimates for the Lives Saved Tool (LiST). Meta-analysis was performed if appropriate. For interventions with low quality evidence but strong recommendation for implementation, a Delphi panel was convened to estimate effect size. We identified 24 studies of neonatal resuscitation reporting mortality outcomes (20 observational, 2 quasi-experimental, 2 cluster randomized controlled trials), but none of immediate newborn assessment and stimulation alone. A meta-analysis of three facility-based studies examined the effect of resuscitation training on intrapartum-related neonatal deaths (RR= 0.70, 95%CI 0.59-0.84); this estimate was used for the effect of facility-based basic neonatal resuscitation (additional to stimulation). The evidence for preterm mortality effect was low quality and thus expert opinion was sought. In community-based studies, resuscitation training was part of packages with multiple concurrent interventions, and/or studies did not distinguish term intrapartum-related from preterm deaths, hence no meta-analysis was conducted. Our Delphi panel of 18 experts estimated that immediate newborn assessment and stimulation would reduce both intrapartum-related and preterm deaths by 10%, facility-based resuscitation would prevent a further 10% of preterm deaths, and community-based resuscitation would prevent further 20% of intrapartum-related and 5% of preterm deaths. Neonatal resuscitation training in facilities reduces term intrapartum-related deaths by 30%. Yet, coverage of this intervention remains low in countries where most neonatal deaths occur and is a missed opportunity to save lives. Expert opinion supports smaller effects of neonatal resuscitation on preterm mortality in facilities and of basic resuscitation and newborn assessment and stimulation at community level. Further evaluation is required for impact, cost and implementation strategies in various contexts. This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to the Saving Newborn Lives program of Save the Children, through Save the Children US.

Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

Abstract: Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke.

Patterns and dynamics of dissolved organic carbon (DOC) in boreal streams: The role of processes, connectivity, and scaling

Abstract: We bring together three decades of research from a boreal catchment to facilitate an improved mechanistic understanding of surface water dissolved organic carbon (DOC) regulation across multiple scales. The Krycklan Catchment Study encompasses 15 monitored nested research catchments, ranging from 3 to 6900 ha in size, as well as a set of monitored transects of forested and wetland soils. We show that in small homogenous catchments, hydrological functioning provides a first order control on the temporal variability of stream water DOC. In larger, more heterogeneous catchments, stream water DOC dynamics are regulated by the combined effect of hydrological mechanisms and the proportion of major landscape elements, such as wetland and forested areas. As a consequence, streams with heterogeneous catchments undergo a temporal switch in the DOC source. In a typical boreal catchment covered by 10-20% wetlands, DOC originates predominantly from wetland sources during low flow conditions. During high flow, the major source of DOC is from forested areas of the catchment. We demonstrate that by connecting knowledge about DOC sources in the landscape with detailed hydrological process understanding, an improved representation of stream water DOC regulation can be provided. The purpose of this study is to serve as a framework for appreciating the role of regulating mechanisms, connectivity and scaling for understanding the pattern and dynamics of surface water DOC across complex landscapes. The results from this study suggest that the sensitivity of stream water DOC in the boreal landscape ultimately depends on changes within individual landscape elements, the proportion and connectivity of these affected landscape elements, and how these changes are propagated downstream.

Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In the first 5 parts of the AmericanAcademy of Dermatology Psoriasis Guidelines of Care, we have presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In this sixth and final section of the Psoriasis Guidelines of Care, we will present cases to illustrate how to practically use these guidelines in specific clinical scenarios. We will describe the approach to treating patients with psoriasis across the entire spectrum of this fascinating disease from mild to moderate to severe, with and without psoriatic arthritis, based on the 5 prior published guidelines. Although specific therapeutic recommendations are given for each of the cases presented, it is important that treatment be tailored to meet individual patients' needs. In addition, we will update the prior 5 guidelines and address gaps in research and care that currently exist, while making suggestions for further studies that could be performed to help address these limitations in our knowledge base.

Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes.

Abstract: BACKGROUND: We define chronic traumatic encephalopathy (CTE) as a progressive neurodegenerative syndrome caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. OBJECTIVE: We present emerging histomorphologic phenotypes of CTE that we identified in our cohort of CTE cases with apolipoprotein E genotyping and causes and manners of death. METHODS: Autopsy brain tissue of 14 professional athletes and 3 high school football players was examined after unexpected deaths. Histochemical and immunohistochemical tissue staining was performed with apolipoprotein E genotyping. RESULTS: Ten of 14 professional athletes (71%) were positive for CTE: 7 of 8 football players, 2 of 4 wrestlers, and 1 boxer. One of 3 high school players manifested incipient CTE. The age range of those with CTE was 18 to 52 years; they were all male athletes. In all cases of CTE, Alzheimer-type cerebral cortical atrophy was absent; negligible to mild neocortical neuronal dropout was present. The fundamental neuropathologic feature of CTE was the topographic distribution of sparse, moderate, and frequent band-shaped, flame-shaped, small and large globose neurofibrillary tangles and neuritic threads in the cerebral cortex, subcortical nuclei/basal ganglia, hippocampus, and brainstem nuclei. Sparse to frequent diffuse amyloid plaques may accompany tauopathy and was seen in only 2 CTE cases. No α-synucleinopathy was present. All 7 CTE-positive professional athletes with known apolipoprotein E genotypes had at least 1 E3 allele comprising 5 E3/E3 (71%) and 2 E3/E4 (29%). Alcohol- and drug-related deaths, suicides, and accidental deaths were overrepresented in our CTE cohort. CONCLUSION: The emerging histomorphologic features of our CTE cohort may specify histologic criteria for CTE diagnosis, may identify emerging histologic variants of CTE and may facilitate more objective surveillance and accurate identification of sentinel CTE cases. Language: en

From forest to field: Perennial fruit crop domestication

Abstract: PREMISE OF THE STUDY Archaeological and genetic analyses of seed-propagated annual crops have greatly advanced our understanding of plant domestication and evolution. Comparatively little is known about perennial plant domestication, a relevant topic for understanding how genes and genomes evolve in long-lived species, and how perennials respond to selection pressures operating on a relatively short time scale. Here, we focus on long-lived perennial crops (mainly trees and other woody plants) grown for their fruits. KEY RESULTS We reviewed (1) the basic biology of long-lived perennials, setting the stage for perennial domestication by considering how these species evolve in nature; (2) the suite of morphological features associated with perennial fruit crops undergoing domestication; (3) the origins and evolution of domesticated perennials grown for their fruits; and (4) the genetic basis of domestication in perennial fruit crops. CONCLUSIONS Long-lived perennials have lengthy juvenile phases, extensive outcrossing, widespread hybridization, and limited population structure. Under domestication, these features, combined with clonal propagation, multiple origins, and ongoing crop-wild gene flow, contribute to mild domestication bottlenecks in perennial fruit crops. Morphological changes under domestication have many parallels to annual crops, but with key differences for mating system evolution and mode of reproduction. Quantitative trait loci associated with domestication traits in perennials are mainly of minor effect and may not be stable across years. Future studies that take advantage of genomic approaches and consider demographic history will elucidate the genetics of agriculturally and ecologically important traits in perennial fruit crops and their wild relatives.

Obstructive sleep apnea devices for out-of-center (OOC) testing: technology evaluation.

Abstract: Guidance is needed to help clinicians decide which out-of-center (OOC) testing devices are appropriate for diagnosing obstructive sleep apnea (OSA). A new classification system that details the type of signals measured by these devices is presented. This proposed system categorizes OOC devices based on measurements of Sleep, Cardiovascular, Oximetry, Position, Effort, and Respiratory (SCOPER) parameters.Criteria for evaluating the devices are also presented, which were generated from chosen pre-test and post-test probabilities. These criteria state that in patients with a high pretest probability of having OSA, the OOC testing device has a positive likelihood ratio (LR+) of 5 or greater coinciding with an in-lab-polysomnography (PSG)-generated apnea hypopnea index (AHI) ≥ 5, and an adequate sensitivity (at least 0.825).Since oximetry is a mandatory signal for scoring AHI using PSG, devices that do not incorporate oximetry were excluded. English peer-reviewed literature on FDA-approved devices utilizing more than 1 signal was reviewed according to the above criteria for 6 questions. These questions specifically addressed the adequacy of different respiratory and effort sensors and combinations thereof to diagnose OSA. In summary, the literature is currently inadequate to state with confidence that a thermistor alone without any effort sensor is adequate to diagnose OSA; if a thermal sensing device is used as the only measure of respiration, 2 effort belts are required as part of the montage and piezoelectric belts are acceptable in this context; nasal pressure can be an adequate measurement of respiration with no effort measure with the caveat that this may be device specific; nasal pressure may be used in combination with either 2 piezoelectric or respiratory inductance plethysmographic (RIP) belts (but not 1 piezoelectric belt); and there is insufficient evidence to state that both nasal pressure and thermistor are required to adequately diagnose OSA. With respect to alternative devices for diagnosing OSA, the data indicate that peripheral arterial tonometry (PAT) devices are adequate for the proposed use; the device based on cardiac signals shows promise, but more study is required as it has not been tested in the home setting; for the device based on end-tidal CO(2) (ETCO(2)), it appears to be adequate for a hospital population; and for devices utilizing acoustic signals, the data are insufficient to determine whether the use of acoustic signals with other signals as a substitute for airflow is adequate to diagnose OSA.Standardized research is needed on OOC devices that report LR+ at the appropriate AHI (≥ 5) and scored according to the recommended definitions, while using appropriate research reporting and methodology to minimize bias.

Association Between Biologic Therapies for Chronic Plaque Psoriasis and Cardiovascular Events: A Meta-analysis of Randomized Controlled Trials

Abstract: Context Ustekinumab and briakinumab, monoclonal antibodies to the shared p40 subunit of interleukin (IL)-12 and IL-23, have shown efficacy in treating chronic plaque psoriasis (CPP). Preliminary reports of major adverse cardiovascular events (MACEs) in psoriasis patients receiving anti–IL-12/23 agents have prompted concern. Objective To evaluate a possible association between biologic therapies for CPP and MACEs via meta-analysis. Data Sources Randomized controlled trials (RCTs) of anti–IL-12/23 (ustekinumab and briakinumab) agents and anti–tumor necrosis factor α (TNF-α) agents (adalimumab, etanercept, and infliximab) used in treating CPP were reviewed using the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Ovid MEDLINE from database inception to May 2011. The results of registered nonpublished completed studies were procured through abstract publications or poster presentations. Study Selection Randomized, placebo-controlled, double-blind, monotherapy studies (with safety outcome data for MACE) of IL-12/23 antibodies and anti–TNF-α agents in adults. Studies of psoriatic arthritis were excluded. Data Extraction Two investigators independently searched data while 6 investigators reviewed the abstracted data. Results A total of 22 RCTs comprising 10 183 patients met the predefined inclusion criteria. The primary outcome measure was MACE, a composite end point of myocardial infarction, cerebrovascular accident, or cardiovascular death during the placebo-controlled phase of treatment in patients receiving at least 1 dose of study agent or placebo. Absolute risk differences were used as an effect measure. There was no evidence of statistical heterogeneity across the studies using the I 2 statistic (I 2 = 0), allowing for combination of trial results using the Mantel-Haenszel fixed-effects method. During the placebo-controlled phases of the anti–IL-12/23 studies, 10 of 3179 patients receiving anti–IL-12/23 therapies experienced MACEs compared with zero events in 1474 patients receiving placebo (Mantel-Haenszel risk difference, 0.012 events/person-year; 95% confidence interval [CI], −0.001 to 0.026; P =.12). In the anti–TNF-α trials, only 1 of 3858 patients receiving anti–TNF-α agents experienced a MACE compared with 1 of 1812 patients receiving placebo (Mantel-Haenszel risk difference, −0.0005 events/person-year; 95% CI, −0.010 to 0.009; P = .94). Conclusions Compared with placebo, there was no significant difference in the rate of MACEs observed in patients receiving anti–IL-12/IL-23 antibodies or anti–TNF-α treatments. This study may have been underpowered to identify a significant difference.

Live and Inactivated Influenza Vaccines Induce Similar Humoral Responses, but Only Live Vaccines Induce Diverse T-Cell Responses in Young Children

Abstract: Background. Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children ($24 months old for LAIV and $6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons. Methods. Children 6‐35 months old were administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were measured by hemagglutination inhibition (HAI), and T cells were studied in flow cytometric and functional assays. Highly conserved M1, M2, and NP peptides predicted to be presented by common HLA class I and II were used to stimulate interferon-c enzyme-linked immunospot responses. Results. All LAIV and/or TIV combinations were well tolerated and induced similar HAI responses. In contrast, only regimens containing LAIV induced influenza-specific CD4 1 , CD8 1 , and cdT cells, including T cells specific for highly conserved influenza peptides. Conclusions. Prime/boost combinations of LAIV and TIV in young children were safe and induced similar protective antibodies. Only LAIV induced CD4 1 ,C D8 1 ,a ndcd T cells relevant for broadly protective heterosubtypic immunity.

Genetic calibration of species diversity among North America's freshwater fishes

Abstract: Freshwater ecosystems are being heavily exploited and degraded by human activities all over the world, including in North America, where fishes and fisheries are strongly affected. Despite centuries of taxonomic inquiry, problems inherent to species identification continue to hamper the conservation of North American freshwater fishes. Indeed, nearly 10% of species diversity is thought to remain undescribed. To provide an independent calibration of taxonomic uncertainty and to establish a more accessible molecular identification key for its application, we generated a standard reference library of mtDNA sequences (DNA barcodes) derived from expert-identified museum specimens for 752 North American freshwater fish species. This study demonstrates that 90% of known species can be delineated using barcodes. Moreover, it reveals numerous genetic discontinuities indicative of independently evolving lineages within described species, which points to the presence of morphologically cryptic diversity. From the 752 species analyzed, our survey flagged 138 named species that represent as many as 347 candidate species, which suggests a 28% increase in species diversity. In contrast, several species of parasitic and nonparasitic lampreys lack such discontinuity and may represent alternative life history strategies within single species. Therefore, it appears that the current North American freshwater fish taxonomy at the species level significantly conceals diversity in some groups, although artificially creating diversity in others. In addition to providing an easily accessible digital identification system, this study identifies 151 fish species for which taxonomic revision is required.

Hepcidin in Human Iron Disorders: Diagnostic Implications

Abstract: BACKGROUND: The peptide hormone hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. Many human diseases are associated with alterations in hepcidin concentrations. The measurement of hepcidin in biological fluids is therefore a promising tool in the diagnosis and management of medical conditions in which iron metabolism is affected. CONTENT: We describe hepcidin structure, kinetics, function, and regulation. We moreover explore the therapeutic potential for modulating hepcidin expression and the diagnostic potential for hepcidin measurements in clinical practice. SUMMARY: Cell-culture, animal, and human studies have shown that hepcidin is predominantly synthesized by hepatocytes, where its expression is regulated by body iron status, erythropoietic activity, oxygen tension, and inflammatory cytokines. Hepcidin lowers serum iron concentrations by counteracting the function of ferroportin, a major cellular iron exporter present in the membrane of macrophages, hepatocytes, and the basolateral site of enterocytes. Hepcidin is detected in biologic fluids as a 25 amino acid isoform, hepcidin-25, and 2 smaller forms, i.e., hepcidin-22 and −20; however, only hepcidin-25 has been shown to participate in the regulation of iron metabolism. Reliable assays to measure hepcidin in blood and urine by use of immunochemical and mass spectrometry methods have been developed. Results of proof-of-principle studies have highlighted hepcidin as a promising diagnostic tool and therapeutic target for iron disorders. However, before hepcidin measurements can be used in routine clinical practice, efforts will be required to assess the relevance of hepcidin isoform measurements, to harmonize the different assays, to define clinical decision limits, and to increase assay availability for clinical laboratories.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study

Abstract: Objective To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. Methods This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A–E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. Results Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. Conclusions This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.

The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice

Abstract: Systemic iron homeostasis is mainly controlled by the liver through synthesis of the peptide hormone hepcidin (encoded by Hamp), the key regulator of duodenal iron absorption and macrophage iron release. Here we show that the liver-specific microRNA miR-122 is important for regulating Hamp mRNA expression and tissue iron levels. Efficient and specific depletion of miR-122 by injection of a locked-nucleic-acid-modified (LNA-modified) anti-miR into WT mice caused systemic iron deficiency, characterized by reduced plasma and liver iron levels, mildly impaired hematopoiesis, and increased extramedullary erythropoiesis in the spleen. Moreover, miR-122 inhibition increased the amount of mRNA transcribed by genes that control systemic iron levels, such as hemochromatosis (Hfe), hemojuvelin (Hjv), bone morphogenetic protein receptor type 1A (Bmpr1a), and Hamp. Importantly, miR-122 directly targeted the 3′ untranslated region of 2 mRNAs that encode activators of hepcidin expression, Hfe and Hjv. These data help to explain the increased Hamp mRNA levels and subsequent iron deficiency in mice with reduced miR-122 levels and establish a direct mechanistic link between miR-122 and the regulation of systemic iron metabolism.

Association of Myocardial Enzyme Elevation and Survival Following Coronary Artery Bypass Graft Surgery

Abstract: confidenceinterval[CI],0.36%-1.02%)for0to1,0.86%(95%CI,0.49%-1.40%)for 1t o2, 0.95% (95% CI, 0.72%-1.22%) for 2 to 5, 2.09% (95% CI, 1.69%-2.57%) for5to10,2.78%(95%CI,2.12%-3.58%)for10to20,and7.06%(95%CI,5.46%8.96%) for 20 to 40. Of the variables considered, the CK-MB ratio was the strongest independent predictor of death to 30 days and remained significant even after adjusting for a wide range of baseline risk factors (

Cytokine and Chemokine Responses in Serum and Brain After Single and Repeated Injections of Lipopolysaccharide: Multiplex Quantification with Path Analysis

Abstract: Administration of the proinflammatory molecule lipopolysaccharide (LPS) alters transport rates for many peptides across the blood-brain barrier (BBB). We and others have previously shown that effects of LPS on BBB transport are highly dependent on the injection paradigm used, and timing of the study. Cytokine expression in both brain and serum compartments influence the BBB response to an inflammatory stimulus, and mediate changes in BBB transport. Here, we used multianalyte technology to simultaneously determine the responses of 13 cytokines and chemokines (G-CSF, GM-CSF, IL- 1α, IL-1β, IL-6, IL-10, IL-13, IP-10, KC, MCP-1, MIP-lα, RANTES, and TNF- α) in brain and blood to single and repeated injections of LPS and path analysis to determine the major relations among these analytes. Major findings are: 1) in comparison to measurements taken from a time course after a single injection of LPS, the three injection regimen of LPS produced significantly higher levels in brain for G-CSF, IL-1 alpha, IL-6, MCP-1, MIP-1 alpha, and TNF and in serum for G-CSF, IL-6, and GM-CSF and 2) path analysis distinguished direct from indirect correlations between analyte pairs, with MCP-1, IL-6, G-CSF, and KC mediating relations among these cytokines both within and between serum and brain compartments. These results suggest that potentiation of cytokine levels in brain and serum compartments could play important roles in the regulation of BBB transport, and that our novel application of an established statistical method can be used to assess direct correlations within multiplexed datasets.

One hundred new species of lichenized fungi : a signature of undiscovered global diversity

Abstract: The number of undescribed species of lichenized fungi has been estimated at roughly 10,000. Describing and cataloging these would take the existing number of taxonomists several decades; however, the support for taxonomy is in decline worldwide. In this paper we emphasize the dire need for taxonomic expertise in lichenology. We bring together 103 colleagues from institutions worldwide to describe a total of 100 new species of lichenized fungi, representing a wide taxonomic and geographic range. The newly described species are: Acarospora flavisparsa, A. janae, Aderkomyces thailandicus, Amandinea maritima, Ampliotrema cocosense, Anomomorpha lecanorina, A. tuberculata, Aspicilia mansourii, Bacidina sorediata, Badimia multiseptata, B. vezdana, Biatora epirotica, Buellia sulphurica, Bunodophoron pinnatum, Byssoloma spinulosum, Calopadia cinereopruinosa, C. editae, Caloplaca brownlieae, C. decipioides, C. digitaurea, C. magnussoniana, C. mereschkowskiana, C. yorkensis, Calvitimela uniseptata, Chapsa microspora, C. psoromica, C. rubropulveracea, C. thallotrema, Chiodecton pustuliferum, Cladonia mongkolsukii, Clypeopyrenis porinoides, Coccocarpia delicatula, Coenogonium flammeum, Cresponea ancistrosporelloides, Crocynia microphyllina, Dictyonema hernandezii, D. hirsutum, Diorygma microsporum, D. sticticum, Echinoplaca pernambucensis, E. schizidiifera, Eremithallus marusae, Everniastrum constictovexans, Fellhanera borbonica, Fibrillithecis sprucei, Fissurina astroisidiata, F. nigrolabiata, F. subcomparimuralis, Graphis caribica, G. cerradensis, G. itatiaiensis, G. marusa, Gyalideopsis chicaque, Gyrotrema papillatum, Harpidium gavilaniae, Hypogymnia amplexa, Hypotrachyna guatemalensis, H. indica, H. lueckingii, H. paracitrella, H. paraphyscioides, H. parasinuosa, Icmadophila eucalypti, Krogia microphylla, Lecanora mugambii, L. printzenii, L. xanthoplumosella, Lecidea lygommella, Lecidella greenii, Lempholemma corticola, Lepraria sekikaica, Lobariella sipmanii, Megalospora austropacifica, M. galapagoensis, Menegazzia endocrocea, Myriotrema endoflavescens, Ocellularia albobullata, O. vizcayensis, Ochrolechia insularis, Opegrapha viridipruinosa, Pannaria phyllidiata, Parmelia asiatica, Pertusaria conspersa, Phlyctis psoromica, Placopsis imshaugii, Platismatia wheeleri, Porina huainamdungensis, Ramalina hyrcana, R. stoffersii, Relicina colombiana, Rhizocarpon diploschistidina, Sticta venosa, Sagenidiopsis isidiata, Tapellaria albomarginata, Thelotrema fijiense, Tricharia nigriuncinata, Usnea galapagona, U. pallidocarpa, Verrucaria rhizicola, and Xanthomendoza rosmarieae. In addition, three new combinations are proposed: Fibrillithecis dehiscens, Lobariella botryoides, and Lobariella pallida.