Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis.

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one\u27s risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. Across k=36 independent samples and n=14,991 participants, trauma exposure was positively associated with C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α (mean rs =0.2455, 0.3067, 0.2890, and 0.2998, respectively). No significant relationships were noted with fibrinogen, IL-2, IL-4, IL-8, or IL-10. In meta-regression models, the presence of psychiatric symptoms was a significant predictor of increased effect sizes for IL-1β and IL-6 (β=1.0175 and 0.3568, respectively), whereas study quality assessment scores were associated with increased effect sizes for IL-6 (β=0.3812). Positive correlations between inflammation and trauma exposure across a range of sample types and diagnoses were found. Although reviewed studies spanned an array of populations, research on any one specific psychiatric diagnosis was generally limited to one or two studies. The results suggest that chronic inflammation likely represents one potential mechanism underlying risk of health problems in trauma survivors

Maternal undernutrition and the ovine acute phase response to vaccination

Background: The acute phase response is the immediate host response to infection, inflammation and trauma and can be monitored by measuring the acute phase proteins (APP) such as haptoglobin ( Hp) or serum amyloid A (SAA). The plane of nutrition during pregnancy is known to affect many mechanisms including the neuroendocrine and neuroimmune systems in neonatal animals but effects on the APP are unknown. To investigate this phenomenon the serum concentration of Hp and SAA was initially determined in non-stimulated lambs from 3 groups (n = 10/group). The dams of the lambs of the respective groups were fed 100% of requirements throughout gestation (High/High; HH); 100% of requirements for the first 65 d of gestation followed by 70% of requirements until 125 d from when they were fed 100% of requirements (High/Low; HL); 65% of liveweight maintenance requirements for the first 65 d gestation followed by 100% of requirements for the remainder of pregnancy ( Low/High; LH). The dynamic APP response in the lambs was estimated by measuring the concentration of Hp and SAA following routine vaccination with a multivalent clostridial vaccine with a Pasteurella component, Heptavac P (TM) following primary and secondary vaccination. Results: The Hp and SAA concentrations were significantly lower at the time of vaccination ( day 8-14) than on the day of birth. Vaccination stimulated the acute phase response in lambs with increases found in both Hp and SAA. Maternal undernutrition led to the SAA response to vaccination being significantly lower in the HL group than in the HH group. The LH group did not differ significantly from either the HH or HL groups. No significant effects of maternal undernutrition were found on the Hp concentrations. A significant reduction was found in all groups in the response of SAA following the second vaccination compared to the response after the primary vaccination but no change occurred in the Hp response. Conclusion: Decreased SAA concentrations, post-vaccination, in lambs born to ewes on the HL diet shows that maternal undernutrition prior to parturition affects the innate immune system of the offspring. The differences in response of Hp and SAA to primary and secondary vaccinations indicate that the cytokine driven APP response mechanisms vary with individual AP

An examination of autism spectrum traits in adolescents with anorexia nervosa and their parents

There may be a link between anorexia nervosa and autism spectrum disorders. The aims of this study were to examine whether adolescents with anorexia nervosa have autism spectrum and/or obsessive-compulsive traits, how many would meet diagnostic criteria for autism spectrum disorder, and whether these traits are shared by parents

An examination of the clinical outcomes of adolescents and young adults with broad autism spectrum traits and autism spectrum disorder and anorexia nervosa: A multi centre study

Objectives: To compare the clinical outcomes of adolescents and young adults with anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD traits. Method: The developmental and well‐being assessment and social aptitude scale were used to categorize adolescents and young adults with AN (N = 149) into those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria for a possible/probable ASD (N = 6). We compared both eating disorders specific measures and broader outcome measures at intake and 12 months follow‐up. Results: Those with ASD traits had significantly more inpatient/day‐patient service use (p = .015), as well as medication use (p < .001) at baseline. Both groups had high social difficulties and poorer global functioning (strengths and difficulties questionnaire) at baseline, which improved over time but remained higher at 12 months in the ASD traits group (p = .002). However, the improvement in eating disorder symptoms at 12 months was similar between groups with or without ASD traits. Treatment completion rates between AN only and ASD traits were similar (80.1 vs. 86.5%). Discussion: Adolescents with AN and ASD traits show similar reductions in their eating disorder symptoms. Nevertheless, their social difficulties remain high suggesting that these are life‐long difficulties rather than starvation effects

In utero exposure to cigarette smoke dysregulates human fetal ovarian developmental signalling

STUDY QUESTION How does maternal cigarette smoking disturb development of the human fetal ovary?&lt;p&gt;&lt;/p&gt; SUMMARY ANSWER Maternal smoking increases fetal estrogen titres and dysregulates several developmental processes in the fetal ovary.&lt;p&gt;&lt;/p&gt; WHAT IS KNOWN ALREADY Exposure to maternal cigarette smoking during gestation reduces human fetal ovarian cell numbers, germ cell proliferation and subsequent adult fecundity.&lt;p&gt;&lt;/p&gt; STUDY DESIGN, SIZE, DURATION The effects of maternal cigarette smoking on the second trimester human fetal ovary, fetal endocrine signalling and fetal chemical burden were studied. A total of 105 fetuses were studied, 56 from mothers who smoked during pregnancy and 49 from those who did not.&lt;p&gt;&lt;/p&gt; PARTICIPANTS/MATERIALS, SETTING METHODS Ovary, liver and plasma samples were collected from electively terminated, normally progressing, second trimester human fetuses. Circulating fetal hormones, levels of 73 fetal ovarian transcripts, protein localization, density of oocytes/primordial follicles and levels of 16 polycyclic aromatic hydrocarbons (PAHs) in the fetal liver were determined.&lt;p&gt;&lt;/p&gt; MAIN RESULTS AND THE ROLE OF CHANCE Circulating fetal estrogen levels were very high and were increased by maternal smoking (ANOVA, P = 0.055–0.004 versus control). Smoke exposure also dysregulated (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.046–0.023) four fetal ovarian genes (cytochrome P450 scc [CYP11A1], NOBOX oogenesis homeobox [NOBOX], activator of apoptosis harakiri [HRK], nuclear receptor subfamily 2, group E, member 1 [NR2E1]), shifted the ovarian Inhibin βA/inhibin α ratio (NHBA/INHA) transcript ratio in favour of activin (ANOVA, P = 0.049 versus control) and reduced the proportion of dominant-negative estrogen receptor 2 (ERβ: ESR2) isoforms in half the exposed fetuses. PAHs, ligands for the aryl hydrocarbon receptor (AHR), were increased nearly 6-fold by maternal smoking (ANOVA, P = 0.011 versus control). A fifth transcript, COUP transcription factor 1 (nuclear receptor subfamily 2, group F, member 1: NR2F1, which contains multiple AHR-binding sites), was both significantly increased (ANOVA, P = 0.026 versus control) and dysregulated by (two-way ANOVA, smoking versus gestation weeks interaction, P = 0.021) maternal smoking. NR2F1 is associated with repression of FSHR expression and smoke-exposed ovaries failed to show the normal increase in FSHR expression during the second trimester. There was a significantly higher number of DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 (DDX4) VASA-positive (ANOVA, P = 0.016 versus control), but not POU domain, class 1, transcription factor 1 (POU5F1) OCT3/4-positive, oocytes in smoke-exposed fetuses and this matched with a significantly higher number of primordial follicles (ANOVA, P = 0.024 versus control).&lt;p&gt;&lt;/p&gt; LIMITATIONS, REASONS FOR CAUTION The effects of maternal smoking on establishment of the maximum fetal primordial follicle pool cannot be reliably studied in our population since the process is not completed until 28 weeks of gestation and normal fetuses older than 21 weeks of gestation are not available for study. Our data suggest that some fetal ovaries are affected by smoke exposure while others are not, indicating that additional studies, with larger numbers, may show more significant effects.&lt;p&gt;&lt;/p&gt; WIDER IMPLICATIONS OF THE FINDINGS Fetal exposure to chemicals in cigarette smoke is known to lead to reduced fecundity in women. Our study suggests, for the first time, that this occurs via mechanisms involving activation of AHR, disruption of inhibin/activin and estrogen signalling, increased exposure to estrogen and dysregulation of multiple molecular pathways in the exposed human fetal ovary. Our data also suggest that alterations in the ESR2 positive and dominant negative isoforms may be associated with reduced sensitivity of some fetuses to increased estrogens and maternal smoking

Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.

Open Access articleA poor diet during pregnancy has been linked to long-term health outcomes for the baby, such as an increased risk of diseases of the heart and kidney. We show in an experimental model that recreates a poor diet during pregnancy, i.e. a diet low in protein with adequate energy, that kidney development in the baby is affected in such a way as to reduce the potential for new blood vessels to form. This results in a greater number of important, functional kidney cells spontaneously dying. Later in life, these effects in the kidney manifest as permanently reduced kidney function, especially if the baby subsequently becomes overweight as an adult. The research reinforces advice to pregnant mothers about the importance of eating a nutritionally balanced diet during pregnancy

Initial evidence for the criterion-related and structural validity of the long versions of the direct and meta-perspectives of the Coach-Athlete Relationship Questionnaire

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.The aim of the present study was to develop and initially validate a longer version of the direct (Jowett & Ntoumanis, 2004) and meta-perspectives (Jowett, 2009a, 2009b) of the Coach-Athlete Relationship Questionnaire (CART-Q). In Study 1, instruments (e.g. questionnaires, scales, and inventories) that have been used to assess relationship quality in the broader psychological literature were examined and items potentially relevant to the coach-athlete relationship were identified. The content validity of the identified items was then assessed using expert panels. A final questionnaire was subsequently prepared and administered to 693 participants (310 coaches and 383 athletes). Confirmatory factor analysis was employed to assess the multidimensional nature of the questionnaire based on the 3Cs (i.e. closeness, commitment, and complementarity) model of the coach-athlete relationship. The findings indicated that the direct and meta-perspective items of the long versions of the CART-Q approached an adequate data fit. Moreover, evidence for the internal consistency and criterion validity of the new instruments was also obtained. In Study 2, the newly developed measure was administered to an independent sample of 251 individuals (145 athletes and 106 coaches). Further statistical support was gained for the factorial validity and reliability of the longer version of the CART-Q

Vocation, Belongingness, and Balance: A Qualitative Study of Veterinary Student Well-Being

An elevated risk for suicide among veterinarians has stimulated research into the mental health of the veterinary profession, and more recently attention has turned to the veterinary student population. This qualitative study sought to explore UK veterinary students' perceptions and experiences of university life, and to consider how these may affect well-being. Semi-structured interviews were conducted with 18 students from a single UK school who were purposively selected to include perspectives from male, female, graduate-entry, standard-entry (straight from high school), and widening participation students across all 5 years of the program. Three main themes were identified: a deep-rooted vocation, navigating belongingness, and finding balance. Participants described a long-standing goal of becoming a veterinarian, with a determination reflected by often circuitous routes to veterinary school and little or no consideration of alternatives. Although some had been motivated by a love of animals, others were intrinsically interested in the scientific and problem-solving challenges of veterinary medicine. Most expressed strong feelings of empathy with animal owners. The issue of belongingness was central to participants' experiences, with accounts reflecting their efforts to negotiate a sense of belongingness both in student and professional communities. Participants also frequently expressed a degree of acceptance of poor balance between work and relaxation, with indications of a belief that this imbalance could be rectified later. This study helps highlight future avenues for research and supports initiatives aiming to nurture a sense of collegiality among veterinary students as they progress through training and into the profession

Endogenous U2.U5.U6 snRNA complexes in S. pombe are intron lariat spliceosomes

Excision of introns from pre-mRNAs is mediated by the spliceosome, a multi-megadalton complex consisting of U1, U2, U4/U6, and U5 snRNPs plus scores of associated proteins. Spliceosome assembly and disassembly are highly dynamic processes involving multiple stable intermediates. In this study, we utilized a split TAP-tag approach for large-scale purification of an abundant endogenous U2.U5.U6 complex from Schizosaccharomyces pombe. RNAseq revealed this complex to largely contain excised introns, indicating that it is primarily ILS (intron lariat spliceosome) complexes. These endogenous ILS complexes are remarkably resistant to both high-salt and nuclease digestion. Mass spectrometry analysis identified 68, 45, and 43 proteins in low-salt-, high-salt-, and micrococcal nuclease-treated preps, respectively. The protein content of a S. pombe ILS complex strongly resembles that previously reported for human spliced product (P) and Saccharomyces cerevisiae ILS complexes assembled on single pre-mRNAs in vitro. However, the ATP-dependent RNA helicase Brr2 was either substoichiometric in low-salt preps or completely absent from high-salt and MNase preps. Because Brr2 facilitates spliceosome disassembly, its relative absence may explain why the ILS complex accumulates logarithmically growing cultures and the inability of S. pombe extracts to support in vitro splicing