Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD.

OBJECTIVE: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). METHOD: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. RESULTS: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (α > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. CONCLUSION: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment

Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata

Breathing is highly sensitive to the PCO2 of arterial blood. Although CO2 is detected via the proxy of pH, CO2 acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally link the direct sensing of CO2 to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Differential CpG DNA methylation in peripheral naïve CD4+ T-cells in early rheumatoid arthritis patients

Background: The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation, one of the hallmarks of epigenetic re-programing, as well as many T-cell genes, with a strong MHC association, pointing to immunogenetic mechanisms as disease triggers leading to chronicity. The aim of our study was to explore DNA methylation in early, drug-naïve RA patients, towards a better understanding of early events in pathogenesis. Result: Monocytes, naïve and memory CD4+ T-cells were sorted from 6 healthy controls and 10 RA patients. DNA methylation was assessed using a genome-wide Illumina 450K CpG promoter array. Differential methylation was confirmed using bisulfite sequencing for a specific gene promoter, ELISA for several cytokines and flow cytometry for cell surface markers. Differentially methylated (DM) CpGs were observed in 1047 genes in naïve CD4+ T-cells, 913 in memory cells and was minimal in monocytes with only 177 genes. Naive CD4+ T-cells were further investigated as presenting differential methylation in the promoter of > 500 genes associated with several disease-relevant pathways, including many cytokines and their receptors. We confirmed hypomethylation of a region of the TNF-alpha gene in early RA and differential expression of 3 cytokines (IL21, IL34 and RANKL). Using a bioinformatics package (DMRcate) and an in-house analysis based on differences in β values, we established lists of DM genes between health and RA. Publicly available gene expression data were interrogated to confirm differential expression of over 70 DM genes. The lists of DM genes were further investigated based on a functional relationship database analysis, which pointed to an IL6/JAK1/STAT3 node, related to TNF-signalling and engagement in Th17 cell differentiation amongst many pathways. Five DM genes for cell surface markers (CD4, IL6R, IL2RA/CD25, CD62L, CXCR4) were investigated towards identifying subpopulations of CD4+ T-cells undergoing these modifications and pointed to a subset of naïve T-cells, with high levels of CD4, IL2R, and CXCR4, but reduction and loss of IL6R and CD62L, respectively. Conclusion: Our data provided novel conceptual advances in the understanding of early RA pathogenesis, with implications for early treatment and prevention

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Provision of obstetrics and gynaecology services during the COVID-19 pandemic:a survey of junior doctors in the UK National Health Service

Objective: The COVID-19 pandemic is disrupting health services worldwide. We aimed to evaluate the provision of obstetrics and gynaecology services in the UK during the acute-phase of the COVID-19 pandemic. Design: Interview-based national survey. Setting: Women’s healthcare units in the National Health Service. Population: Junior doctors in obstetrics and gynaecology. Methods: Participants were interviewed by members of the UKARCOG trainees’ collaborative between 28th March and 7th of April 2020. We used a quantitative analysis for closed-ended questions and a thematic framework analysis for open comments. Results: We received responses from 148/155 units (95%), majority of the participants were in years 3-7 of training (121/148, 82%). Most completed specific training drills for managing obstetric and gynaecological emergencies in women with COVID-19 (89/148, 60.1%) and two-persons donning and doffing of Personal Protective Equipment (PPE) (96/148, 64.9%). The majority of surveyed units implemented COVID-19 specific protocols (130/148, 87.8%), offered adequate PPE (135/148, 91.2%) and operated dedicated COVID-19 emergency theatres (105/148, 70.8%). Most units reduced face-to-face antenatal clinics (117/148, 79.1%), and suspended elective gynaecology services (131/148, 88.5%). The two-week referral pathway for oncology gynaecology was not affected in half of the units (76/148, 51.4%), while half reported a planned reduction in oncology operating (82/148, 55.4%). Conclusion: The provision of obstetrics and gynaecology services in the UK during the acute phase of the COVID-19 pandemic seems to be in line with current guidelines, but strategic planning is needed to restore routine gynaecology services and ensure safe access to maternity care on the longterm

Feasibility and acceptability of expressive writing with postpartum women: a randomised controlled trial

Abstract Background: Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect women’s mental and physical health. Expressive writing, where people write about a stressful event for at least 15 minutes on three consecutive days, has been associated with improved health in some groups but it is not clear whether it is feasible and acceptable for use with postpartum women. This study therefore examined the feasibility and acceptability of expressive writing for postpartum women as part of a randomised controlled trial (RCT). Methods: The Health After Birth Trial (HABiT) was an RCT evaluating expressive writing for postpartum women which included measures of feasibility and acceptability. At 6 to 12 weeks after birth 854 women were randomised to expressive writing, a control writing task or normal care, and outcome measures of health were measured at baseline, one month later and six months later. Feasibility was measured by recruitment, attrition, and adherence to the intervention. Quantitative and qualitative measures of acceptability of the materials and the task were completed six months after the intervention. Results: Recruitment was low (10.7% of those invited to participate) and the recruited sample was from a restricted sociodemographic range. Attrition was high, increased as the study progressed (35.8% at baseline, 57.5% at one month, and 68.1% at six months) and was higher in the writing groups than in the normal care group. Women complied with instructions to write expressively or not, but adherence to the instruction to write for 15 minutes per day for three days was low (Expressive writing: 29.3%; Control writing: 23.5%). Acceptability measures showed that women who wrote expressively rated the materials/task both more positively and more negatively than those in the control writing group, and qualitative comments revealed that women enjoyed the writing and/or found it helpful even when it was upsetting. Conclusions: The feasibility of offering expressive writing as a universal self-help intervention to all postpartum women 6 to 12 weeks after birth in the HABiT trial was low, but the expressive writing intervention was acceptable to the majority of women who completed it

Revisiting histories of anti-racist thought and activism

This piece reconsiders histories of anti-racist thought and practice, including the linkages between anti-racisms and other traditions of liberatory thought. We argue that anti-racism should be understood as a strand in radical thought linking internationalism, institutional critique and street activism, in the process interfeeding with other social movements. The traditions of anti-racist thought discussed in this special issue exemplify these cross-cutting influences

Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy

<p>Abstract</p> <p>Background</p> <p>We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas.</p> <p>Methods</p> <p>A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the study. These patients were treated with either radiotherapy alone or radiotherapy followed by PCV chemotherapy after surgery. Five prognostic factors, including histological subsets, age, performance status, extent of resection, and treatment modality were incorporated into the RPA. The final nodes of RPA were grouped according to their survival times, and the Kaplan-Meier graphs are presented as the final set of prognostic groups.</p> <p>Results</p> <p>Four risk groups were defined based on the clinical prognostic factors excluding age, and split variables were all incorporated into the RPA. Survival analysis showed significant differences in mean survival between the different groups: 163.4 months (95% CI: 144.9-182.0), 109.5 months (86.7-132.4), 66.6 months (50.8-82.4), and 27.7 months (16.3-39.0), respectively, from the lowest to the highest risk group (p = 0.00).</p> <p>Conclusion</p> <p>The present study shows that RPA grouping with clinical prognostic factors can successfully predict the survival of patients with WHO grade III glioma.</p