Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a ...controlled, cross-sectional, age-matched (18–56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task.
Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and ...appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).
The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
Thirty-five metabolites were strongly associated with prostate cancer (
< 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.
We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.
The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
The role of collagen XII in regulating injury repair and reestablishment of corneal function is unknown. This manuscript aims to investigate the role(s) of collagen XII in the repair of incisional ...and debridement injuries in an adult mouse model. Two different types of injury in wild type and Col12a1−/− corneas were created to investigate the effects of collagen XII -in wound repair and scar formation-by using clinical photographs, immunohistology, second harmonic generation imaging and electron microscopy. Results showed that collagen XII is a regulator of wound closure after incisional injuries. Absence of collagen XII retarded wound closure and the wound healing process. These findings show that collagen XII regulates fibrillogenesis, CD68 cell lineage infiltration, and myofibroblast survival following injury. In vitro studies suggest that collagen XII regulates deposition of an early and provisional matrix by interacting with two proteins regulating early matrix deposition: fibronectin and LTBP1(latent transforming growth factor β binding protein 1). In conclusion, collagen XII regulates tissue repair in corneal incisional wounds. Understanding the function of collagen XII during wound healing has significant translational value.
•Collagen XII is essential to attain wound closure and scar maturation.•Incisional injuries heal poorly and closure is delayed without collagen XII.•Collagen XII is deposited early during wound closure.•Collagen XII interacts with other matrix components of the provisional matrix
Abstract
Successful research and development requires interdisciplinary collaboration, often across organisational boundaries and for extended timeframes, such as in innovation networks or ...ecosystems. Open Organisation (OO) research can support collaboration and knowledge exchange in such situations. It builds on established concepts of Open Innovation through enhancing the exchange of knowledge by the exchange of humans. This paper contributes to OO research by presenting an OO lifecycle framework, which analyses evolving organisational and collaboration characteristics and resulting management needs.
IMPORTANCE: A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data ...regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. OBJECTIVE: To generate core domains and domain items for a global network of alopecia areata patient registries. EVIDENCE REVIEW: Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019. FINDINGS: Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented. CONCLUSIONS AND RELEVANCE: This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.
Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of ...hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects. Fine-mapping reduced the genomic intervals and gene content, and the introgression of one QTL region back onto the C57BL/6J-Chr 1(A/J)/NaJ restored the trait. mRNA expression of non-synonymous genes in the introgressed region in the medulla and pons found evidence for differential expression of three genes, the highest of which was apolipoprotein A2, a lipase regulator; the apo a2 peptide fragment (THEQLTPLVR), highly expressed in the liver, was expressed in low amounts in the medulla but did not correlate with trait expression. This work directly demonstrates the impact of elements on mouse chromosome 1 in respiratory rhythmogenesis.
Background Randomised controlled trials have shown exercise benefits people’s general health. For individuals living with Rheumatoid Arthritis (RA), various factors may influence their ability or ...willingness to exercise (Maradit-Kremers et al., 2005; Wolfe et al., 2008). Objectives The aim of this study was to gain an understanding of the perceptions and beliefs about the ability to exercise in people with RA. Methods Six participants aged between 39-76 years with various stages of RA were recruited from the National Rheumatoid Arthritis Society (NRAS). A focus group lasting 60 minutes was run to explore people’s perceptions and beliefs about exercising with RA. Questions had been derived from relevant literature and had been piloted. The focus group was recorded and transcribed verbatim and thematic analysis was used to code the data and identify pertinent themes. Results Seven distinct themes were identified. These were; the belief that specific symptoms prevented exercise, medication modifies the ability to exercise; frustration from not being able to take exercise; benefits of taking exercise; limitations to participation during exercise class; fear of pain or catching colds/infection and conflict in advice from health professionals. All six participants reported they understood the benefits of exercise and each enjoyed taking an appropriate form of exercise. All participants agreed that certain types of exercise could improve their muscle strength but believed that dynamic and weight-bearing exercise would damage their joints. Conclusions The findings suggest that people with RA want to exercise and believe that their medication helps them achieve this. However it was evident that people with RA receive conflicting advice from health care professionals about what is appropriate exercise and alongside fear of pain, joint damage and infection could limit people’s willingness to engage with exercise. References Maradit-Kremers H, Crowson C, Nicola P Ballman KV, roger VL, Jacobson SJ, Gabriel SE (2005). Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis and Rheumatism 52: 402–411. Wolfe F, Michaud K (2008) The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: a cohort and nested case control analysis. Arthritis Rheumatology 58: 2612-2621 DOI: 10.1002/art.23811. Acknowledgements I am grateful to Dr J Adams and Dr M Donovan-Hall for supervising this project and allowing me to perform my studies within the Faculty of Health Sciences, University of Southampton, and providing continual support, advice and encouragement throughout the project. I would like to thank Hannah Haywood for all the assistance given to me. Ailsa Bosworth Chief Director, National Rheumatoid Arthritis Society, for all their support and thank you to the participants whom without their co-operation I would not have succeeded with this project. Disclosure of Interest None Declared
The purpose of this study was to investigate methods used to modulate dose distributions in radiotherapy planning, to determine the fundamental features of these and to establish the attainable dose ...uniformity. Published modulation methods were categorized, and a simple physical model devised to predict the weight of the wedged beam and the relative dose distribution for each category. Each technique was applied to patient data with planning target volume sizes ranging from below 500 cm(3) to 2200 cm(3). The spatial distribution of high-dose regions in the breast, and maximum dose for the heart and lung, were determined for each plan. The dose uniformity was analysed by evaluating the volume of the breast (V(I)) receiving <95% and <105% of the prescribed dose. The difference between V(105%) and V(95%) for each method for each patient data set was also calculated. The simple model predicted the trend in percentage weight of the wedge beam and the form of the dose distribution in the transverse plane with the modulation method. Improvements in the dose uniformity were seen for the majority of modulation methods. The magnitude of the change was between 5.6% and 11.1% (p<0.05) of the breast volume for breast sizes above 500 cm(3). Some modulation methods introduced high dose at the chest wall. In conclusion, the majority of the methods improved dose uniformity for breast sizes of 500 cm(3) or greater. No method showed a clear advantage over the others. The use of modulation methods should be governed by consideration of its effects relative to a simple wedge plan.
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