Characteristics of individuals with insomnia who seek treatment in a clinical setting versus those who volunteer for a randomized controlled trial

The generalizability of outcome data derived from insomnia clinical trials is based largely on the extent to which research volunteers resemble clinical patients. This study compared sociodemographic, sleep, psychological, and medical characteristics of individuals who volunteered for an insomnia treatment study (n = 120) to patients who sought treatment in a clinical setting (n = 106). The samples did not differ on most sleep and medical variables, but clinical patients had a higher prevalence of mood disorders, greater anxiety and depression symptoms, and higher perceived insomnia severity. Differences on psychological variables were accentuated by the research selection process. It is suggested to minimize exclusion based on psychological comorbidity in order to enhance ecological validity of randomized controlled trials of insomnia treatments

The SIMS trial:adjustable anchored single-incision mini-slings versus standard tension-free midurethral slings in the surgical management of female stress urinary incontinence. A study protocol for a pragmatic, multicentre, non-inferiority randomised controlled trial

This is a UK Collaborative Study funded by the NIHR Evaluation, Health Technology Assessment (HTA) Programme — Funder Number 12/127/157.Peer reviewedPublisher PD

Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study

BACKGROUND: When a patient is approaching death in the intensive care unit (ICU), patients' relatives must make a rapid transition from focusing on their beloved one's recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Net

Runx Expression Is Mitogenic and Mutually Linked to Wnt Activity in Blastula-Stage Sea Urchin Embryos

The Runt homology domain (Runx) defines a metazoan family of sequence-specific transcriptional regulatory proteins that are critical for animal development and causally associated with a variety of mammalian cancers. The sea urchin Runx gene SpRunt-1 is expressed throughout the blastula stage embryo, and is required globally during embryogenesis for cell survival and differentiation.Depletion of SpRunt-1 by morpholino antisense-mediated knockdown causes a blastula stage deficit in cell proliferation, as shown by bromodeoxyuridine (BrdU) incorporation and direct cell counts. Reverse transcription coupled polymerase chain reaction (RT-PCR) studies show that the cell proliferation deficit is presaged by a deficit in the expression of several zygotic wnt genes, including wnt8, a key regulator of endomesoderm development. In addition, SpRunt-1-depleted blastulae underexpress cyclinD, an effector of mitogenic Wnt signaling. Blastula stage cell proliferation is also impeded by knockdown of either wnt8 or cyclinD. Chromatin immunoprecipitation (ChIP) indicates that Runx target sites within 5′ sequences flanking cyclinD, wnt6 and wnt8 are directly bound by SpRunt-1 protein at late blastula stage. Furthermore, experiments using a green fluorescent protein (GFP) reporter transgene show that the blastula-stage operation of a cis-regulatory module previously shown to be required for wnt8 expression (Minokawa et al., Dev. Biol. 288: 545–558, 2005) is dependent on its direct sequence-specific interaction with SpRunt-1. Finally, inhibitor studies and immunoblot analysis show that SpRunt-1 protein levels are negatively regulated by glycogen synthase kinase (GSK)-3.These results suggest that Runx expression and Wnt signaling are mutually linked in a feedback circuit that controls cell proliferation during development

The HAPPY (Healthy and Active Parenting Programmme for early Years) feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity.

The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY).A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m(2)) were recruited between 10-26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant's length and weight, woman's BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content.Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1-12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of -0.25 standard deviation scores for infant weight at 12 months (95 % CI: -0.16-0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported.The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial.Current Controlled Trials ISRCTN56735429

Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

Peer reviewe

Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity

Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 µm. Cell enlargement was observed in vivo, producing cells up to 100 µm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aΔ pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection

A Comparison of Methods to Harmonize Cortical Thickness Measurements Across Scanners and Sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects

Assessment of Brain Age in Posttraumatic Stress Disorder: Findings from the ENIGMA PTSD and Brain Age Working Groups

Background Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method Adult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site. Results BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. Discussion Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan