Schizotypy and Risk-Taking Behaviour: the Contribution of Urgency

The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) defines schizotypy as a multidimensional psychopathology construct comprising Unusual Experiences, Cognitive Disorganisation, Impulsive Nonconformity, and Introvertive Anhedonia. Previous research indicates that schizotypy is associated with various risky behaviours. Urgency (emotional impulsivity) has a unique and clinically important effect on risk-taking. However, the interplay between schizotypy and urgency in relation to risk-taking has not received adequate consideration. A sample of 204 participants completed self-report scales measuring Schizotypy, Urgency and Risk-taking behaviour. Using structural equation modelling, a mediational model tested the degree to which O-LIFE subfactors directly and indirectly (via urgency) predicted self-reported likelihood to engage in Risk-taking behaviour. Results indicated that Cognitive Disorganisation and Introvertive Anhedonia negatively predicted engagement in Risk-taking behaviour, whereas Impulsive Nonconformity positively predicted engagement in Risk-taking behaviour. Unusual Experiences, Cognitive Disorganisation and Impulsive Nonconformity had indirect effects on Risk-taking through Urgency. Inclusion of Urgency added explanatory power to the schizotypy-risk relationship

Allograft donor characteristics significantly influence graft rupture after anterior cruciate ligament reconstruction in a young active population

Background: Graft selection in anterior cruciate ligament (ACL) surgery can be difficult in a young active population given their high rates of reinjury. Allografts allow for control over graft size and reduce morbidity of autograft harvest. There are mixed results about the use of allograft in the literature; however, the influence of the properties of the allograft on outcomes has not been considered. Hypothesis: ACL reconstruction with allografts from older donors will have a higher rate of graft rupture when compared with allograft from young donors. Study Design: Cohort study; Level of evidence, 3. Methods: Patients (N = 211) aged 13 to 25 years underwent primary ACL reconstruction with fresh-frozen nonirradiated allograft. Four graft types were used: patellar tendon, Achilles tendon, tibialis anterior, and tibialis posterior. Details were collected on allograft donor age and sex. At a minimum of 24 months, patients were evaluated for any further injuries and subjective analysis by International Knee Documentation Committee (IKDC) questionnaire. Results: ACL graft rupture occurred in 23.5%. When grafts were separated into single strand (patellar and Achilles tendon) and multistrand (tibialis anterior and posterior), there was a significantly higher rate of reinjury in the single-strand grafts (29.9% vs 11%; P = .014). Grafts from female donors aged ≥50 years had significantly higher rates of ACL graft rupture (52.6%; P = .003) with increased odds by 6.7 times when compared with grafts from male donors aged donor. Conclusion: The age and sex of the allograft donor and the morphology of the graft significantly influenced the rate of ACL graft rupture in young active patients. Tendons from female donors aged ≥50 years should be avoided given the higher rerupture rates as compared with male donors of any age and younger females

Repeat anterior cruciate ligament injury and return to sport in Australian soccer players after anterior cruciate ligament reconstruction with hamstring tendon autograft

Background: Soccer is the most commonly played team sport in the world and a high-risk sport for anterior cruciate ligament (ACL) injury and subsequent ACL reconstruction (ACLR). Purpose: To assess the rate of further ACL injury in patients who have undergone ACLR with hamstring tendon autograft after soccer injuries in Australia and to determine factors associated with repeat ACL injury and return to soccer. Study Design: Case-control study; Level of evidence, 3. Methods: From a prospectively collected database, a series of 1000 consecutive ACLRs using hamstring autografts performed in soccer players were identified. Patients were surveyed at a minimum 5 years after reconstruction, including details of further ACL injuries to either knee, return to soccer or other sports, and psychological readiness per the Anterior Cruciate Ligament Return to Sport after Injury (ACL-RSI) scale. Results: Of the 862 participants reviewed, ACL graft rupture occurred in 85 (10%) and contralateral ACL rupture in 68 (8%) within 5 years after the reconstruction. The 5-year ACL graft survivorship was 94% for females and 88% for males. The survivorship of the contralateral ACL was 92% for males and 90% for females. When compared with those aged \u3e25 years, the odds of ACL graft rupture was increased by 4 to 5 times in those aged 19 to 25 years and 3 to 7 times in those ≤18 years. Further ACL injury to the graft or contralateral knee occurred in 44% of males aged ≤18 years. Risk factors for further ACL injury were younger age at time of surgery, male sex, and return to soccer. Graft diameter did not influence ACL graft rupture rates, and 70% of patients returned to soccer after ACLR. The mean ACL-RSI score was 59, and patients who reported more fear of reinjury on this scale were less likely to have returned to soccer. Conclusion: The prevalence of ACL graft rupture (10%) and contralateral ACL rupture (8%) was near equivalent over 5 years in this large cohort of mostly recreational Australian soccer players. ACLR with hamstring autograft is a reliable procedure, allowing 70% of patients to return to soccer in this high-risk population. Risk factors for further ACL injury are progressively younger age at time of surgery, male sex, and return to soccer. Graft diameter was not a factor in ACL graft rupture, indicating that other factors, particularly age, are of primary importance

Excitation of emission lines by fluorescence and recombination in IC 418

We predict intensities of lines of CII, NI, NII, OI and OII and compare them with a deep spectroscopic survey of IC 418 to test the effect of excitation of nebular emission lines by continuum fluorescence of starlight. Our calculations use a nebular model and a synthetic spectrum of its central star to take into account excitation of the lines by continuum fluorescence and recombination. The NII spectrum is mostly produced by fluorescence due to the low excitation conditions of the nebula, but many CII and OII lines have more excitation by fluorescence than recombination. In the neutral envelope, the NI permitted lines are excited by fluorescence, and almost all the OI lines are excited by recombination. Electron excitation produces the forbidden optical lines of OI, but continuum fluorescence excites most of the NI forbidden line intensities. Lines excited by fluorescence of light below the Lyman limit thus suggest a new diagnostic to explore the photodissociation region of a nebula.Comment: 2 pages, 4 figures, to appear in proceedings of the IAU Symposium 283: "Planetary Nebulae: An Eye to the Future", Eds.: A. Manchado, L. Stanghellini and D. Schoenberne

Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial

PURPOSEIn the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.PATIENTS AND METHODSA total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (gBRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed gBRCAmut (non?gBRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to gBRCAmut status and response to their last platinum-based therapy. Ovarian cancer?specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy?Ovarian Symptom Index.RESULTSProgression-free survival was improved in patients treated with niraparib compared with placebo in both the gBRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non?gBRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes.CONCLUSIONPatients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy

Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections

Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type–like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read amplicon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections.A.H. is supported by the H2020-MSCA-Global Fellowship (Grant 657766). Doherty Applied Microbial Genomics is funded by the Department of Microbiology and Immunology at The University of Melbourn

A Minimal Functional Complex of Cytochrome P450 and FBD of Cytochrome P450 Reductase in Nanodiscs

Structural interactions that enable electron transfer to cytochromeâ P450 (CYP450) from its redox partner CYP450â reductase (CPR) are a vital prerequisite for its catalytic mechanism. The first structural model for the membraneâ bound functional complex to reveal interactions between the fullâ length CYP450 and a minimal domain of CPR is now reported. The results suggest that anchorage of the proteins in a lipid bilayer is a minimal requirement for CYP450 catalytic function. Akin to cytochromeâ b5 (cytâ b5), Argâ 125 on the Câ helix of CYP450s is found to be important for effective electron transfer, thus supporting the competitive behavior of redox partners for CYP450s. A general approach is presented to study proteinâ protein interactions combining the use of nanodiscs with NMR spectroscopy and SAXS. Linking structural details to the mechanism will help unravel the xenobiotic metabolism of diverse microsomal CYP450s in their native environment and facilitate the design of new drug entities.Auf der Grundlage einer Strukturanalyse von Cytochrom P450 (CYP450) im Komplex mit seinem Redoxpartner kann der Pfad des selektiven Elektronentransfers verstanden werden. Strukturelle Wechselwirkungen in einem solchen Komplex, verankert in einer Lipidmembran, sind eine Grundvoraussetzung für diese Funktion. Der Stoffwechsel von Wirkâ und Fremdstoffen durch diverse mikrosomale CYPs in ihrem nativen Membranumfeld wird aufgeklärt.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/1/ange201802210.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/2/ange201802210-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144609/3/ange201802210_am.pd

Behavioral Coping Phenotypes and Associated Psychosocial Outcomes of Pregnant and Postpartum Women During the COVID-19 Pandemic

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic