Changes in Severity of Pelvic Floor Dysfunction after Hip Surgery

Introduction: Despite growing evidence that suggests an association between hip pathology and pelvic floor disorder (PFD), the comprehensive effects of hip surgery on PFD symptoms are not well understood. The primary purpose of this study was to report the role of surgical hip procedures on the severity of PFD symptoms. Methods: A prospective database of demographic and outcome data for all female patients that were operated on between 2019-2020 at a single institution was queried. The PDFI-20 was used to assess symptom severity, and cases with both pre and postoperative surveys were included (n=62). MCID was used to determine significance of change in PDFI-20 score. Results: All patients were female and mean age was 50.1 years. 40 patients had a THA, 10 had a PAO, 9 had a hip arthroscopy, 2 had a surgical hip dislocation, and one had abductor repair and reconstruction. The pre- and postoperative PFDI-20 scores for patients who underwent THA were 40.4±40.1 and 31.5±35.8. The pre- and post-operative PFDI-20 scores for patients who underwent PAO were 10.6±16.9 and 5.3±12.4. The pre- and post-operative PFDI-20 scores for patients who underwent hip arthroscopy were 7.2±12 and 15.2±25.9. The pre- and post-operative PFDI-20 scores for patients who underwent surgical hip dislocation were 41.7±58.9 and 39.1±55.2. The pre- and post-operative PFDI-20 scores for patients who underwent abductor repair and reconstruction were 33.3±0 and 113.5±0. Conclusion: A subset of patients undergoing hip surgery do have baseline pelvic floor dysfunction. We did not find a significant improvement from pre and post op in our patient population. Mean PFDI-20 scores improved in patients who underwent THA, PAO, and surgical hip dislocation. This study demonstrates that the impact of hip surgery on PFD symptoms in patients with hip pathology should be considered, with further research required to fully characterize this relationship

Arts and creative activities for mental wellbeing during Covid-19 lockdown: report of a survey of university staff

Purpose: There is evidence that the recent Covid-19 pandemic has led to an increase in stress in the UK workforce. Research also suggests that engaging in arts and creative activities may alleviate stress. The purpose was to explore how this might relate to staff at Canterbury Christ Church University, and specifically: 1) to identify the overall extent of uptake and popularity of different arts activities; 2) to assess how this compares with pre-Covid levels of engagement and; 3) to identify how engagement with activities may serve to mitigate any adverse effects of the pandemic and beyond. Design: The two-stage design comprised an online questionnaire, followed by in-depth interviews with a sub-sample of respondents. Findings: 178 individuals responded to the questionnaire, and 12 individuals were interviewed. Receptive arts engagement featured more frequently than participatory arts. 46.6% respondents reported more engagement during lockdown than before. The most frequently reported benefits related to the ability to disengage from the negative concerns of lockdown. Interview data identified four themes: creativity for wellbeing; connecting and contributing; pandemic as opportunity; and reflecting the times. Originality: Little previous research has been conducted on the impacts of the arts specifically on university staff during Covid, particularly research including non-academic staff

Comparison of Audiovisual and Paper-Based Materials for 1-Time Informed Consent for Research in Prison: A Randomized Clinical Trial.

Importance Few studies are available on informed consent (IC) among detained persons, even with ethics being a critical aspect of prison research. In IC research, audiovisual material seems to improve understanding and satisfaction compared with conventional paper-based material, but findings remain unclear. Objective To compare audiovisual and paper-based materials for 1-time general IC for research in prisons. Design, Setting, and Participants This cross-sectional randomized clinical trial was conducted in 2 corrections facilities in Switzerland (an adult prison and a juvenile detention center). The study was conducted from December 14, 2019, to December 2, 2020, in the adult prison and from January 15, 2020, to September 9, 2021, in the juvenile detention center. In the adult prison, study participation was offered to detained persons visiting the medical unit (response rate, 84.7%). In the juvenile detention center, all newly incarcerated adolescents were invited to participate (response rate, 98.0%). Interventions Participants were randomized to receive paper-based conventional material or to watch a 4-minute video. Materials included the same legal information, as required by the Swiss Federal Act on Research Involving Human Beings. Main Outcomes and Measures The main outcome was acceptance to sign the IC form. Secondary outcomes included understanding, evaluation, and time to read or watch the IC material. Results The study included 190 adults (mean [SD] age, 35.0 [11.8] years; 190 [100%] male) and 100 adolescents (mean [SD] age, 16.0 [1.1] years; 83 [83.0%] male). In the adult prison, no significant differences were found between groups in acceptance to sign the IC form (77 [81.1%] for paper-based material and 81 [85.3%] for audiovisual material; P = .39) and to evaluate it (mean [SD] correct responses, 5.09 [1.13] for paper-based material and 5.01 [1.07] for audiovisual material; P = .81). Understanding was significantly higher in the audiovisual material group (mean [SD] correct responses, 5.09 [1.84]) compared with the paper-based material group (mean [SD] correct responses, 4.61 [1.70]; P = .04). In the juvenile detention center, individuals in the audiovisual material group were more likely to sign the IC form (44 [89.8%]) than the paper-based material group (35 [68.6%], P = .006). No significant difference was found between groups for understanding and evaluation. Adults took a mean (SD) of 5 (2) minutes to read the paper material, and adolescents took 7 (3) minutes. Conclusions and Relevance Given the small benefit of audiovisual material, these findings suggest that giving detained adults and prison health care staff a choice regarding IC material is best. For adolescents, audiovisual material should be provided. Future studies should focus on increasing understanding of the IC process. Trial Registration ClinicalTrials.gov Identifier: NCT05505058

Mechanisms controlling the guidance of thalamocortical axons through the embryonic forebrain: Mechanisms controlling the guidance of thalamocortical axons

Thalamocortical axons must cross a complex cellular terrain through the developing forebrain and this terrain has to be understood for us to learn how thalamocortical axons reach their destinations. Selective fasciculation, guidepost cells, various diencephalic and telencephalic gradients have been implicated in thalamocortical guidance. As our understanding of the relevant forebrain patterns has increased, so has out knowledge of the guidance mechanisms. Our aim here is to review recent observations of cellular and molecular mechanisms relating to: the growth of thalamofugal projections to the ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension into the telencephalon to form the internal capsule, the crossing of the pallial-subpallial boundary and the growth towards the cerebral cortex. We shall review current theories for the explanation of the maintenance and alteration of topographic order in the thalamocortical projections to the cortex. It is now increasingly clear that several mechanisms are involved at different stages of thalamocortical development and each contributes substantially to the eventual outcome. Revealing the molecular and cellular mechanisms can help to link specific genes to details of actual developmental mechanisms

Multisite Binding of a General Anesthetic to the Prokaryotic Pentameric Erwinia chrysanthemi Ligand-gated Ion Channel (ELIC)

Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABAA/C receptors, and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anesthetics. Here, we report the x-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore and equates with a noncompetitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7–β10 strands. Together, these results extend our understanding of pLGIC modulation and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multisite model of allosteric modulation in this family of ion channels

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging

Objective: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response. Methods: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. Results: Thirty-five participants completed, on average, 85 hours (IQR=70–100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen’s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. Conclusions: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. Trial registration number: NCT02540889

Infectious Events Prior to Chemotherapy Initiation in Children with Acute Myeloid Leukemia

Background:The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia.Methods:We conducted a retrospective, population-based cohort study that included children and adolescents with acute myeloid leukemia diagnosed and treated at 15 Canadian centers. We evaluated infections that occurred between presentation to the healthcare system (for symptoms that led to the diagnosis of acute myeloid leukemia) until initiation of chemotherapy.Results:Among 328 children, 92 (28.0%) were neutropenic at presentation. Eleven (3.4%) had sterile-site microbiologically documented infection and four had bacteremia (only one Gram negative). Infection rate was not influenced by neutropenia. No child died from an infectious cause prior to chemotherapy initiation.Conclusion:It may be reasonable to withhold empiric antibiotics in febrile non-neutropenic children with newly diagnosed acute myeloid leukemia until initiation of chemotherapy as long as they appear well without a clinical focus of infection. Future work could examine biomarkers or a clinical score to identify children presenting with leukemia and fever who are more likely to have an invasive infection. © 2013 Portwine et al

Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer?s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.FUNDING: Acknowledgements The authors are grateful to the participants in the Religious Order Study, the Memory and Aging Project. Z.C. and R.H.R. were supported by grants from the Leonard Wolfson Foundation. M.R. was supported by the United Kingdom Medical Research Council (MRC) through the award of a Tenure Track Clinician Scientist Fellowship (MR/ N008324/1). J.H. was supported by the UK Dementia Research Institute which receives its funding from DRI Limited, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.H. has also been funded by the Medical Research Council (award MR/N026004/1), Wellcome Trust (award 202903/Z/16/Z), Dolby Family Fund and National Institute for Health Research University College London Hospitals Biomedical Research Centre. J.B. is supported through the Science and Technology Agency, Séneca Foundation, CARM, Spain (research project 00007/COVI/20)

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML

Association between corticosteroids and infection, sepsis, and infectious death in pediatric acute myeloid leukemia (AML): Results from the Canadian infections in AML research group

Background. Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML.Methods. We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates abstracted all information from each site.Results. 341 patients were included. Median age was 7.1 years (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26 (7.6%) experienced death as a first event. There were 1277 courses of chemotherapy administered in which sterile site microbiologically documented infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression analysis, duration of corticosteroid exposure was significantly associated with more microbiologically documented sterile site infection, bacteremia, fungal infection, and sepsis. The only factor significantly associated with infectious death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P =. 001).Conclusions. In pediatric AML, infection, sepsis, and infectious death were associated with duration of corticosteroid exposure. Corticosteroids should be avoided when possible for this population. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved