Major depression, fibromyalgia and labour force participation: A population-based cross-sectional study

BACKGROUND: Previous studies have documented an elevated frequency of depressive symptoms and disorders in fibromyalgia, but have not examined the association between this comorbidity and occupational status. The purpose of this study was to describe these epidemiological associations using a national probability sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey. The prevalence of major depression in subjects reporting that they had been diagnosed with fibromyalgia by a health professional was estimated, and then stratified by demographic variables. Logistic regression models predicting labour force participation were also examined. RESULTS: The annual prevalence of major depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI 19.4 – 24.9), than in those without this condition: 7.2% (95% CI 7.0 – 7.4). The association persisted despite stratification for demographic variables. Logistic regression models predicting labour force participation indicated that both conditions had an independent (negative) effect on labour force participation. CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be related to each other at a pathophysiological level. However, each syndrome is independently and negatively associated with labour force participation. A strength of this study is that it was conducted in a large probability sample from the general population. The main limitations are its cross-sectional nature, and its reliance on self-reported diagnoses of fibromyalgia

Duloxetine in the treatment of major depressive disorder: an open-label study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.</p> <p>Methods</p> <p>Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD₁₇) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD₁₇total score, HAMD₁₇subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.</p> <p>Results</p> <p>The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD₁₇, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.</p> <p>Conclusion</p> <p>In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.</p> <p>Trial registration</p> <p>NCT00036309.</p

Semi-automatic conversion of BioProp semantic annotation to PASBio annotation

<p>Abstract</p> <p>Background</p> <p>Semantic role labeling (SRL) is an important text analysis technique. In SRL, sentences are represented by one or more predicate-argument structures (PAS). Each PAS is composed of a predicate (verb) and several arguments (noun phrases, adverbial phrases, etc.) with different semantic roles, including main arguments (agent or patient) as well as adjunct arguments (time, manner, or location). PropBank is the most widely used PAS corpus and annotation format in the newswire domain. In the biomedical field, however, more detailed and restrictive PAS annotation formats such as PASBio are popular. Unfortunately, due to the lack of an annotated PASBio corpus, no publicly available machine-learning (ML) based SRL systems based on PASBio have been developed. In previous work, we constructed a biomedical corpus based on the PropBank standard called BioProp, on which we developed an ML-based SRL system, BIOSMILE. In this paper, we aim to build a system to convert BIOSMILE's BioProp annotation output to PASBio annotation. Our system consists of BIOSMILE in combination with a BioProp-PASBio rule-based converter, and an additional semi-automatic rule generator.</p> <p>Results</p> <p>Our first experiment evaluated our rule-based converter's performance independently from BIOSMILE performance. The converter achieved an F-score of 85.29%. The second experiment evaluated combined system (BIOSMILE + rule-based converter). The system achieved an F-score of 69.08% for PASBio's 29 verbs.</p> <p>Conclusion</p> <p>Our approach allows PAS conversion between BioProp and PASBio annotation using BIOSMILE alongside our newly developed semi-automatic rule generator and rule-based converter. Our system can match the performance of other state-of-the-art domain-specific ML-based SRL systems and can be easily customized for PASBio application development.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey

BACKGROUND: Middle ear disease (otitis media) is common and frequently severe in Australian Aboriginal children. There have not been any recent large-scale surveys using clear definitions and a standardised middle ear assessment. The aim of the study was to determine the prevalence of middle ear disease (otitis media) in a high-risk population of young Aboriginal children from remote communities in Northern and Central Australia. METHODS: 709 Aboriginal children aged 6–30 months living in 29 communities from 4 health regions participated in the study between May and November 2001. Otitis media (OM) and perforation of the tympanic membrane (TM) were diagnosed by tympanometry, pneumatic otoscopy, and video-otoscopy. We used otoscopic criteria (bulging TM or recent perforation) to diagnose acute otitis media. RESULTS: 914 children were eligible to participate in the study and 709 were assessed (78%). Otitis media affected nearly all children (91%, 95%CI 88, 94). Overall prevalence estimates adjusted for clustering by community were: 10% (95%CI 8, 12) for unilateral otitis media with effusion (OME); 31% (95%CI 27, 34) for bilateral OME; 26% (95%CI 23, 30) for acute otitis media without perforation (AOM/woP); 7% (95%CI 4, 9) for AOM with perforation (AOM/wiP); 2% (95%CI 1, 3) for dry perforation; and 15% (95%CI 11, 19) for chronic suppurative otitis media (CSOM). The perforation prevalence ranged from 0–60% between communities and from 19–33% between regions. Perforations of the tympanic membrane affected 40% of children in their first 18 months of life. These were not always persistent. CONCLUSION: Overall, 1 in every 2 children examined had otoscopic signs consistent with suppurative ear disease and 1 in 4 children had a perforated tympanic membrane. Some of the children with intact tympanic membranes had experienced a perforation that healed before the survey. In this high-risk population, high rates of tympanic perforation were associated with high rates of bulging of the tympanic membrane

Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells

Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function—it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.American Cancer Society (Robbie Sue Mudd Kidney Cancer Research Scholar Grant RSG-13-396-01-RMC)National Institutes of Health (U.S.) (GM094303)National Institutes of Health (U.S.) (GM081399)American Cancer Society. New England Division (Ellison Foundation Postdoctoral Fellowship)American Cancer Society (Postdoctoral Fellowship PF-13-319-01-RMC)National Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

BACKGROUND: The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. METHODS: MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. RESULTS: Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. CONCLUSIONS: This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection

Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1x10(2), 1x10(4), and 1x10(6) inclusion forming units (IFUs). Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4(+) and CD8(+) cells within guinea pigs' submandibular lymph node (SMLN) lymphocytes while the higher doses increased the percentages of CD4(+) and CD8(+) cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4(+) and CD8(+) cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1x10(4), and 1x10(6) IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections

Physician attitude toward depression care interventions: Implications for implementation of quality improvement initiatives

<p>Abstract</p> <p>Background</p> <p>Few individuals with depression treated in the primary care setting receive care consistent with clinical treatment guidelines. Interventions based on the chronic care model (CCM) have been promoted to address barriers and improve the quality of care. A current understanding of barriers to depression care and an awareness of whether physicians believe interventions effectively address those barriers is needed to enhance the success of future implementation.</p> <p>Methods</p> <p>We conducted semi-structured interviews with 23 primary care physicians across the US regarding their experience treating patients with depression, barriers to care, and commonly promoted CCM-based interventions. Themes were identified from interview transcripts using a grounded theory approach.</p> <p>Results</p> <p>Six barriers emerged from the interviews: difficulty diagnosing depression, patient resistance, fragmented mental health system, insurance coverage, lack of expertise, and competing demands and other responsibilities as a primary care provider. A number of interventions were seen as helpful in addressing these barriers – including care managers, mental health integration, and education – while others received mixed reviews. Mental health consultation models received the least endorsement. Two systems-related barriers, the fragmented mental health system and insurance coverage limitations, appeared incompletely addressed by the interventions.</p> <p>Conclusion</p> <p>CCM-based interventions, which include care managers, mental health integration, and patient education, are most likely to be implemented successfully because they effectively address several important barriers to care and are endorsed by physicians. Practices considering the adoption of interventions that received less support should educate physicians about the benefit of the interventions and attend to physician concerns prior to implementation. A focus on interventions that address systems-related barriers is needed to overcome all barriers to care.</p