Negative Interpretation Bias and the Experience of Pain in Adolescents

Negative interpretation bias, the tendency to appraise ambiguous situations in a negative or threatening way, has been suggested to be important for the development of adult chronic pain. This is the first study to examine the role of a negative interpretation bias in adolescent pain. We first developed and piloted a novel task that measures the tendency for adolescents to interpret ambiguous situations as indicative of pain and bodily threat. Using this task in a separate community sample of adolescents (N=115), we then found that adolescents who catastrophize about pain, as well as those who reported more pain issues in the preceding three months, were more likely to endorse negative interpretations, and less likely to endorse benign interpretations, of ambiguous situations. This interpretation pattern was not, however, specific for situations regarding pain and bodily threat, but generalized across social situations as well. We also found that a negative interpretation bias, specifically in ambiguous situations that could indicate pain and bodily threat, mediated the association between pain catastrophizing and recent pain experiences. Findings may support one potential cognitive mechanism explaining why adolescents who catastrophize about pain often report more pain. Perspective This article presents a new adolescent measure of interpretation bias. We found that the tendency to interpret ambiguous situations as indicative of pain and bodily threat may be one potential cognitive mechanism explaining why adolescents who catastrophize about pain report more pain, thus indicating a potential novel intervention target.</p

Depression, anxiety, stress, social interaction and health-related quality of life in men and women with unexplained chest pain

<p>Abstract</p> <p>Background</p> <p>Unexplained chest pain (UCP) is a common reason for emergency hospital admission and generates considerable health-care costs for society. Even though prior research indicates that psychological problems and impaired quality of life are common among UCP patients, there is lack of knowledge comparing UCP patients with a reference group from the general population. The aim of this study was to analyse differences between men and women with UCP and a reference group in terms of psychosocial factors as depression, anxiety, stress, social interaction and health-related quality of life (HRQOL).</p> <p>Methods</p> <p>A self-administered questionnaire about psychosocial factors was completed by 127 men and 104 women with acute UCP admitted consecutively to the Emergency Department (ED) or as in-patients on a medical ward. A reference group from the general population, 490 men and 579 women, participants in the INTERGENE study and free of clinical heart disease, were selected.</p> <p>Results</p> <p>The UCP patients were more likely to be immigrants, have a sedentary lifestyle, report stress at work and have symptoms of depression and trait-anxiety compared with the reference group. After adjustment for differences in age, smoking, hypertension and diabetes, these factors were still significantly more common among patients with UCP. In a stepwise multivariate model with mutual adjustment for psychosocial factors, being an immigrant was associated with a more than twofold risk in both sexes. Stress at work was associated with an almost fourfold increase in risk among men, whereas there was no independent impact for women. In contrast, depression only emerged as an independent risk factor in women. Trait-anxiety and a low level of social interaction were not independently associated with risk in either men or women. Patients with UCP were two to five times more likely to have low scores for HRQOL.</p> <p>Conclusion</p> <p>Both men and women with UCP had higher depression scores than referents, but an independent association was only found in women. Among men, perceived stress at work emerged as the only psychosocial variable significantly associated with UCP.</p

Improving knowledge of breastfeeding management: A practice development intervention for paediatric nurses

Aim The primary aim of this study was to evaluate the impact of a targeted, practical education intervention on paediatric nurses' knowledge of appropriate breastfeeding management in an acute practice setting. Background Breastfeeding provides the optimal method for infant growth and nutrition, yet studies have demonstrated knowledge deficits of Australian paediatric nurses regarding the management of the mother-infant breastfeeding dyad. Limited evidence is available evaluating which educational approach is effective in the dynamic and busy acute care setting. Design This study was a two-phased, mixed-method design, conducted in a large, tertiary, metropolitan children's hospital in south-east Queensland, Australia. Methods Reference groups were conducted in Phase One to advise development of the resource kit. Phase Two was the experimental phase and included a pre-test knowledge survey, the educational intervention, and a post-test knowledge survey. Results Pre- and post-test response rates of 75% (n=49) and 34% (n=23) respectively were achieved from the population of 67 eligible participants. Post-intervention study results demonstrated knowledge improvement in four key breastfeeding management areas: importance of baby-led feeding; reduction in otitis media risk for breastfed infants; ongoing management of maternal milk supply when breastfeeding is interrupted; and the correct storage and management of expressed breast milk. Areas for further knowledge improvement included management of more complex breastfeeding scenarios, such as mastitis. Conclusion The implementation of a resource kit and brief education series has improved the knowledge of paediatric nurses in some areas of breastfeeding practice and management

Impact of Different Flushing Frequencies on Peripheral Intravenous Catheter Failure, Coagulation, and Tissue Injury - A Counterbalanced Preclinical Human Trial

Background:Peripheral intravenous venous catheters (PIVCs) are associated with a postinsertion failure incidence of 40%, yet the common maintenance and preventive strategy of saline flushing is poorly understood at a physiological level.Methods:We developed a human model of bilateral cephalic vein cannulation to study the impact of varied PIVC flushing frequency (high frequency, HF; low frequency, LF) over 5 hours on catheter failure (primary outcome), coagulation, platelet aggregation, and local tissue injury. Ultrasound was used in a subset to assess vascular diameter/catheter to vein, blood flow velocity, and thrombus formation.Results:Out of 34 catheters in 17 adult participants, 1/17 (6%) LF catheters failed, which was not significantly different from HF catheters (0/17). Platelet function, activated partial thromboplastin time, and tissue factor were also not different (P > 0.05). However, prothrombin time (PT) increased with HF versus LF after 5 hours (P Conclusions:Although no difference in PIVC failure was observed between HF and LF flushing conditions over 5 hours, greater flushing frequency increased PT time, suggesting delayed activation or consumption of extrinsic coagulation factors. This study also demonstrated feasibility in assessment of luminal thromboses, which were remarkably prevalent after PIVC placement, and changes in vascular diameter and blood flow. This manuscript illustrates that the development of a sensitive human model will be of great use for exploring the impact of interventions on reducing PIVC failure in the future

HDBR Expression: A Unique Resource for Global and Individual Gene Expression Studies during Early Human Brain Development

This paper describes a new resource, HDBR (Human Developmental Biology Resource) Expression, for studying prenatal human brain development. It is unique in the age range (4 post conception weeks [PCW] to 17PCW) and number of brains (172) studied, particularly those under 8PCW (33). The great majority of the samples are karyotyped. HDBR Expression is also unique in that both the large-scale data sets (RNA-seq data, SNP genotype data) and the corresponding RNA and DNA samples are available, the latter via the MRC-Wellcome Trust funded HDBR1(Gerrelli et al., 2015). There are 557 RNA-seq datasets from different brain regions, the majority between 4 and 12PCW. During this time the major brain regions are established and the early stages of cortex development occur (Bystron et al., 2008; O'Rahilly and Muller, 2008). In addition, there are 42 RNAseq data sets from spinal cord and 29 from cerebral choroid plexus. There are also 243 additional tissue specimens in paraffin wax blocks available for individual gene expression studies. For almost all of the brains and specimens in wax blocks there are corresponding SNP genotype data. Large-scale/high-throughput studies, such as next-generation sequencing, are providing raw material in a wide variety of research fields (for review of concepts and methodologies of RNA-seq, see Shin et al., 2014). Studies of human development are hampered by difficulties in obtaining tissue which means that publicly available large-scale data sets are particularly useful because data can be used and re-used (Kang et al., 2011; Zhang et al., 2011; Fietz et al., 2012; Miller et al., 2014; Darmanis et al., 2015)

Naturally occurring antibodies isolated from PD patients inhibit synuclein seeding in vitro and recognize Lewy pathology

Deposition of α-synuclein into Lewy bodies and Lewy neurites is the hallmark of Parkinson’s disease (PD). It is hypothesized that α-synuclein pathology spreads by a “prion-like” mechanism (i.e., by seeded aggregation or templated misfolding). Therefore, various extracellular α-synuclein conformers and/or posttranslational modifications may serve as biomarkers of disease or potential targets for novel interventions. To explore whether the antibody repertoires of PD patients contain anti-α-synuclein antibodies that can potentially be used as markers or immunotherapy, we interrogated peripheral IgG + memory B cells from PD patients for reactivity to α-synuclein. In total, ten somatically mutated antibodies were recovered, suggesting the presence of an ongoing antigen-driven immune response. The three antibodies that had the highest affinity to recombinant full-length α-synuclein, aSyn-323.1, aSyn-336.1 and aSyn-338.1, were characterized further and shown to recognize epitopes in the C terminus of α-synuclein with binding affinities between 0.3 and 2.8 μM. Furthermore, all three antibodies were able to neutralize the “seeding” of intracellular synuclein aggregates in an in vitro α-synuclein seeding assay. Finally, differential reactivities were observed for all three human anti-α-synuclein antibodies across tissue treatment conditions by immunohistochemistry. Our results suggest that the memory B-cell repertoire of PD patients might represent a potential source of biomarkers and therapies

Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment

With the emergence of checkpoint blockade and other immunotherapeutic drugs, and the growing adoption of smaller, more flexible adaptive clinical trial designs, there is an unmet need to develop diagnostics that can rapidly immunophenotype patient tumors. The ability to longitudinally profile the tumor immune infiltrate in response to immunotherapy also presents a window of opportunity to illuminate mechanisms of resistance. We have developed a fine needle aspirate biopsy (FNA) platform to perform immune profiling on thoracic malignancies. Matching peripheral blood, bulk resected tumor, and FNA were analyzed from 13 mesothelioma patients. FNA samples yielded greater numbers of viable cells when compared to core needle biopsies. Cell numbers were adequate to perform flow cytometric analyses on T cell lineage, T cell activation and inhibitory receptor expression, and myeloid immunosuppressive checkpoint markers. FNA samples were representative of the tumor as a whole as assessed by head-to-head comparison to single cell suspensions of dissociated whole tumor. Parallel analysis of matched patient blood enabled us to establish quality assurance criteria to determine the accuracy of FNA procedures to sample tumor tissue. FNA biopsies provide a diagnostic to rapidly phenotype the tumor immune microenvironment that may be of great relevance to clinical trials

Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance.

Disruption of the adaptor protein SH2B1 (SH2-B, PSM) is associated with severe obesity, insulin resistance, and neurobehavioral abnormalities in mice and humans. Here, we identify 15 SH2B1 variants in severely obese children. Four obesity-associated human SH2B1 variants lie in the Pleckstrin homology (PH) domain, suggesting that the PH domain is essential for SH2B1's function. We generated a mouse model of a human variant in this domain (P322S). P322S/P322S mice exhibited substantial prenatal lethality. Examination of the P322S/+ metabolic phenotype revealed late-onset glucose intolerance. To circumvent P322S/P322S lethality, mice containing a two-amino acid deletion within the SH2B1 PH domain (ΔP317, R318 [ΔPR]) were studied. Mice homozygous for ΔPR were born at the expected Mendelian ratio and exhibited obesity plus insulin resistance and glucose intolerance beyond that attributable to their increased adiposity. These studies demonstrate that the PH domain plays a crucial role in how SH2B1 controls energy balance and glucose homeostasis

Shortening cardioplegic arrest time in patients undergoing combined coronary and valve surgery: results from a multicentre randomized controlled trial: the SCAT trial

OBJECTIVES: Combined coronary artery bypass grafting and valve surgery requires a prolonged period of cardioplegic arrest (CA) predisposing to myocardial injury and postoperative cardiac-specific complications. The aim of this trial was to reduce the CA time in patients undergoing combined coronary artery bypass grafting and valve surgery and assess if this was associated with less myocardial injury and related complications. METHODS: Participants were randomized to (i) coronary artery bypass grafting performed on the beating heart with cardiopulmonary bypass support followed by CA for the valve procedure (hybrid) or (ii) both procedures under CA (conventional). To assess complications related to myocardial injury, we used the composite of death, myocardial infarction, arrhythmia, need for pacing or inotropes for &gt;12 h. To assess myocardial injury, we used serial plasma troponin T and markers of metabolic stress in myocardial biopsies. RESULTS: Hundred and sixty patients (80 hybrid and 80 conventional) were randomized. Mean age was 66.5 years and 74% were male. Valve procedures included aortic (61.8%) and mitral (33.1%) alone or in combination (5.1%). CA time was 16% lower in the hybrid group [median 98 vs 89 min, geometric mean ratio (GMR) 0.84, 95% confidence interval (CI) 0.77–0.93, P = 0.0004]. Complications related to myocardial injury occurred in 131/160 patients (64/80 conventional, 67/80 hybrid), odds ratio 1.24, 95% CI 0.54–2.86, P = 0.61. Release of troponin T was similar between groups (GMR 1.04, 95% CI 0.87–1.24, P = 0.68). Adenosine monophosphate was 28% lower in the hybrid group (GMR 0.72, 95% CI 0.51–1.02, P = 0.056). CONCLUSIONS: The hybrid procedure reduced the CA time but myocardial injury outcomes were not superior to conventional approach. TRIAL REGISTRATION: ISRCTN65770930