306 research outputs found
Achirality in the low temperature structure and lattice modes of tris(acetylacetonate)iron(iii)
Tris(acetylacteonate) iron(III) is a relatively ubiquitous mononuclear inorganic coordination complex. The bidentate nature of the three acetylacteonate ligands coordinating around a single centre inevitably leads to structural isomeric forms, however whether or not this relates to chirality in the solid state has been questioned in the literature. Variable temperature neutron diffraction data down to T = 3 K, highlights the dynamic nature of the ligand environment, including the motions of the hydrogen atoms. The Fourier transform of the molecular dynamics simulation based on the experimentally determined structure was shown to closely reproduce the low temperature vibrational density of states obtained using inelastic neutron scattering
Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: Design and methods for three linked randomised controlled trials
INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients.
METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention.
ETHICS AND DISSEMINATION: The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website.
TRIAL REGISTRATION NUMBERS: NCT05575128, NCT05685511, NCT05697835, pre-results
Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage
Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03–0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment
Genetic Variations in IL28B and Allergic Disease in Children
Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences
US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report
This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in
Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference
Public health campaigns and obesity - a critique
<p>Abstract</p> <p>Background</p> <p>Controlling obesity has become one of the highest priorities for public health practitioners in developed countries. In the absence of safe, effective and widely accessible high-risk approaches (e.g. drugs and surgery) attention has focussed on community-based approaches and social marketing campaigns as the most appropriate form of intervention. However there is limited evidence in support of substantial effectiveness of such interventions.</p> <p>Discussion</p> <p>To date there is little evidence that community-based interventions and social marketing campaigns specifically targeting obesity provide substantial or lasting benefit. Concerns have been raised about potential negative effects created by a focus of these interventions on body shape and size, and of the associated media targeting of obesity.</p> <p>Summary</p> <p>A more appropriate strategy would be to enact high-level policy and legislative changes to alter the obesogenic environments in which we live by providing incentives for healthy eating and increased levels of physical activity. Research is also needed to improve treatments available for individuals already obese.</p
Dark sectors 2016 Workshop: community report
This report, based on the Dark Sectors workshop at SLAC in April 2016,
summarizes the scientific importance of searches for dark sector dark matter
and forces at masses beneath the weak-scale, the status of this broad
international field, the important milestones motivating future exploration,
and promising experimental opportunities to reach these milestones over the
next 5-10 years
Health care access dimensions and cervical cancer screening in South Africa: analysis of the world health survey.
Background
Cervical cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women in sub-Saharan Africa. Recent recommendations for cervical cancer primary prevention highlight HPV vaccination, and secondary prevention through screening. However, few studies have examined the different dimensions of health care access, and how these may influence screening behavior, especially in the context of clinical preventive services. Methods
Using the 2003 South Africa World Health Survey, we determined the prevalence of cervical cancer screening with pelvic examinations and/or pap smears among women ages 18 years and older. We also examined the association between multiple dimensions of health care access and screening focusing on the affordability, availability, accessibility, accommodation and acceptability components. Results
About 1 in 4 (25.3%, n = 65) of the women who attended a health care facility in the past year got screened for cervical cancer. Screened women had a significantly higher number of health care providers available compared with unscreened women (mean 125 vs.12, p-value Conclusions
Our findings suggest that cost issues (affordability component) and other patient level factors (captured in the acceptability, accessibility and accommodation components) were less important predictors of screening compared with availability of physicians in this population. Meeting cervical cancer screening and HPV vaccination goals will require significant investments in the health care workforce, improving health care worker density in poor and rural areas, and improved training of the existing workforce
Polymorphisms in the Mitochondrial Ribosome Recycling Factor EF-G2mt/MEF2 Compromise Cell Respiratory Function and Increase Atorvastatin Toxicity
Mitochondrial translation, essential for synthesis of the electron transport chain complexes in the mitochondria, is governed by nuclear encoded genes. Polymorphisms within these genes are increasingly being implicated in disease and may also trigger adverse drug reactions. Statins, a class of HMG-CoA reductase inhibitors used to treat hypercholesterolemia, are among the most widely prescribed drugs in the world. However, a significant proportion of users suffer side effects of varying severity that commonly affect skeletal muscle. The mitochondria are one of the molecular targets of statins, and these drugs have been known to uncover otherwise silent mitochondrial mutations. Based on yeast genetic studies, we identify the mitochondrial translation factor MEF2 as a mediator of atorvastatin toxicity. The human ortholog of MEF2 is the Elongation Factor Gene (EF-G) 2, which has previously been shown to play a specific role in mitochondrial ribosome recycling. Using small interfering RNA (siRNA) silencing of expression in human cell lines, we demonstrate that the EF-G2mt gene is required for cell growth on galactose medium, signifying an essential role for this gene in aerobic respiration. Furthermore, EF-G2mt silenced cell lines have increased susceptibility to cell death in the presence of atorvastatin. Using yeast as a model, conserved amino acid variants, which arise from non-synonymous single nucleotide polymorphisms (SNPs) in the EF-G2mt gene, were generated in the yeast MEF2 gene. Although these mutations do not produce an obvious growth phenotype, three mutations reveal an atorvastatin-sensitive phenotype and further analysis uncovers a decreased respiratory capacity. These findings constitute the first reported phenotype associated with SNPs in the EF-G2mt gene and implicate the human EF-G2mt gene as a pharmacogenetic candidate gene for statin toxicity in humans
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