Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.

BACKGROUND: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION: ISRCTN: 10412338. Registration date: October 24, 2019.

Effects of the omega-3 fatty acid DHA on histone and p53 acetylation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) often develops resistance and/or relapses in response to immunochemotherapy. Epigenetic modifiers are frequently mutated in DLBCL, i.e., the lysine (histone) acetyltransferases CREBBP and EP300. Mutations in CBP/p300 can prevent the proper acetylation and activation of (i) enhancer sequences of genes required for essential functions (e.g., germinal center exit and differentiation) and (ii) the tumor suppressor p53. Based on evidence that omega-3 fatty acids (ω-3 FAs) affect histone acetylation in various cancers, we investigated whether ω-3 FA docosahexaenoic acid (DHA) could modify levels of histone and p53 acetylation in three DLBCL cell lines (at different CREBBP/EP300 mutational status) versus normal B cells. Exposure to DHA at clinically attainable doses was shown to significantly alter the genome-wide levels of histone posttranslational modifications in a cell-line-dependent and dose-dependent manner. Although histone acetylation did not increase uniformly, as initially expected, levels of p53 acetylation increased consistently. Quantitative reverse transcription polymerase chain reaction results revealed significant changes in expression of multiple genes, including increased expression of CREBBP and of PRDM1 (required for differentiation into plasma cells or memory B cells). Taken together, our results provide (to our knowledge) the first characterization of the epigenetic effects of ω-3 FAs in DLBCL.

A systematic review evaluating metacognitive beliefs in health anxiety and somatic distress.

PURPOSE: Increasing evidence suggests metacognitive beliefs may underpin transdiagnostic mechanisms maintaining psychopathology. The objective of this systematic review was to evaluate published studies investigating the role of metacognitive beliefs in somatic distress in adult samples. METHOD: A systematic review was conducted, spanning five data bases. Studies meeting eligibility criteria were qualitatively synthesized. RESULTS: Thirty-six studies (N = 12,390) met inclusion criteria with results suggesting a relatively consistent positive relationship between metacognitive beliefs and somatic distress. Both general and syndrome-specific metacognitive beliefs demonstrated relationships with not only emotional distress, but also physical symptoms themselves. CONCLUSIONS: Results are discussed in terms of conceptualizing somatic distress through the Self-Regulatory Executive Function (S-REF) Model. Future research into metacognitive therapy for somatic populations is recommended.

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives.

Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered "self-inflicted", as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.

Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring.

Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the cancer protective effect of canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral tumor growth, and smaller tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against breast cancer after carcinogen exposure.

Improving the donation experience and reducing venipuncture pain by addressing fears among whole-blood and plasma donors.

BACKGROUND: Fear of blood donation is implicated in vasovagal reactions, donor recruitment, and retention. This study examined the extent to which fear among donors is associated with various donor outcomes in an Australian sample, and whether fear can be addressed on-site to reduce adverse reactions and improve the donation experience. STUDY DESIGN AND METHODS: Six hundred and sixty-four donors (age M = 33.4, SD = 12.7; 55% female) participated in a two-center, pragmatic, parallel group, individually randomized controlled trial. Following donor registration and consent, whole-blood (n = 539) and plasma (n = 125) donors were assigned to one of four Conditions: control; fear assessment; fear assessment + brochure; fear assessment + brochure + tailored conversation focused on any self-reported fear and coping strategies. Post-donation questionnaires assessed the donors' experience including positive support, donor self-efficacy, anxiety, fear, venipuncture pain, and vasovagal reactions. RESULTS: Fear among donors predicted higher venipuncture pain, post-donation anxiety, and vasovagal reactions and remained significant after controlling for other established predictors (i.e., total estimated blood volume, age, sex, and donation experience). Mediational analyses showed that exposure to brochures (with or without the tailored conversation) was associated with less pain, with this effect mediated by donor perceptions of more positive support. Venipuncture pain was also associated with vasovagal reactions, reduced likelihood of return within 6 months, and less satisfaction with the donation experience. CONCLUSION: The current results underline the importance of interventions to address fear among both whole-blood and plasma donors to secure the safety and well-being of donors and the blood supply.

Genetic and epigenetic determinants of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that govern the GC reaction and those that drive the progression of DLBCL. A second important insight is that some of the most frequent genetic mutations that occur in DLBCL are those related to chromatin and epigenetics, especially those related to proteins that "write" histone post-translational modifications (PTMs). Mutation or deletion of these epigenetic writers often renders cells unable to epigenetically "switch on" critical gene sets that are required to exit the GC reaction, differentiate, repair DNA, and other essential cellular functions. Failure to activate these genes locks cells into a genotoxic state that is conducive to oncogenesis and/or relapse.

A regularized phase-field model for faceting in a kinetically controlled crystal growth.

At equilibrium, the shape of a strongly anisotropic crystal exhibits corners when for some orientations the surface stiffness is negative. In the sharp-interface problem, the surface free energy is traditionally augmented with a curvature-dependent term in order to round the corners and regularize the dynamic equations that describe the motion of such interfaces. In this paper, we adopt a diffuse interface description and present a phase-field model for strongly anisotropic crystals that is regularized using an approximation of the Willmore energy. The Allen-Cahn equation is employed to model kinetically controlled crystal growth. Using the method of matched asymptotic expansions, it is shown that the model converges to the sharp-interface theory proposed by Herring. Then, the stress tensor is used to derive the force acting on the diffuse interface and to examine the properties of a corner at equilibrium. Finally, the coarsening dynamics of the faceting instability during growth is investigated. Phase-field simulations reveal the existence of a parabolic regime, with the mean facet length evolving in t , with t the time, as predicted by the sharp-interface theory. A specific coarsening mechanism is observed: a hill disappears as the two neighbouring valleys merge.

Glass shape influences drinking behaviours in three laboratory experiments.

Reducing consumption of drinks which contain high levels of sugar and/or alcohol may improve population health. There is increasing interest in health behaviour change approaches which work by changing cues in physical environments ("nudges"). Glassware represents a modifiable cue in the drinking environment that may influence how much we drink. Here, we report three laboratory experiments measuring consumption of soft drinks served in different glasses (straight-sided vs. outward-sloped), using distinct paradigms to measure drinking. In Study 1 (N = 200), though total drinking time was equivalent, participants consumed a soft drink with a more 'decelerated' trajectory from outward-sloped tumblers, characterised by a greater amount consumed in the first half of the drinking episode. In Study 2 (N = 72), during a bogus taste test, participants consumed less from straight-sided wine flutes than outward-sloped martini coupes. In Study 3 (N = 40), using facial electromyography to explore a potential mechanism for decreased consumption, straight-sided glasses elicited more 'pursed' lip embouchures, which may partly explain reduced consumption from these glasses. Using a combination of methods, including objective measures of volume drunk and physiological measures, these findings suggest that switching to straight-sided glasses may be one intervention contributing to the many needed to reduce consumption of health-harming drinks.

Effects of Low-Level Laser Therapy and Chiropractic Care on Back Pain in Quarter Horses.

Low-level laser therapy has been used clinically to treat musculoskeletal pain; however, there is limited evidence available to support its use in treating back pain in horses. The objective of this study was to evaluate the clinical effectiveness of low-level laser therapy and chiropractic care in treating thoracolumbar pain in competitive western performance horses. The subjects included 61 Quarter Horses actively involved in national western performance competitions judged to have back pain. A randomized, clinical trial was conducted by assigning affected horses to either laser therapy, chiropractic, or combined laser and chiropractic treatment groups. Outcome parameters included a visual analog scale (VAS) of perceived back pain and dysfunction and detailed spinal examinations evaluating pain, muscle tone, and stiffness. Mechanical nociceptive thresholds were measured along the dorsal trunk and values were compared before and after treatment. Repeated measures with post-hoc analysis were used to assess treatment group differences. Low-level laser therapy, as applied in this study, produced significant reductions in back pain, epaxial muscle hypertonicity, and trunk stiffness. Combined laser therapy and chiropractic care produced similar reductions, with additional significant decreases in the severity of epaxial muscle hypertonicity and trunk stiffness. Chiropractic treatment by itself did not produce any significant changes in back pain, muscle hypertonicity, or trunk stiffness; however, there were improvements in trunk and pelvic flexion reflexes. The combination of laser therapy and chiropractic care seemed to provide additive effects in treating back pain and trunk stiffness that were not present with chiropractic treatment alone. The results of this study support the concept that a multimodal approach of laser therapy and chiropractic care is beneficial in treating back pain in horses involved in active competition.

Predicting blood donation intention: the importance of fear.

BACKGROUND: Blood donor recruitment remains an important worldwide challenge due to changes in population demographics and shifts in the demand for blood. Various cognitive models help predict donation intention, although the importance of affective deterrents has become increasingly evident. This study aimed to identify fears that predict donation intention, to explore their relative importance, and to determine if self-efficacy and attitude mediate this relationship, thus providing possible targets for intervention. STUDY DESIGN AND METHODS: A total of 347 individuals (269 nondonors and 78 donors) living in Québec responded to questionnaires assessing medical fears, psychosocial factors related to donation intention including the Theory of Planned Behavior (TPB) constructs, anticipated regret, and facilitating factors (i.e., time commitment and rewards). To examine the relative importance of these factors in the context of blood donation, the same questions were also asked about other medical activities that involve salient needle stimuli: flu vaccinations and dental examinations. RESULTS: Medical fears, especially blood-related fears, were significantly associated with donation intention. Bootstrapping tests confirmed that this relation was mediated by attitude and self-efficacy. Underlining the importance of medical fears in the blood donation context, these fears were not associated with attitudes and intentions for dental examinations or flu vaccinations. CONCLUSION: These results suggest that medical fears, especially blood-related fears, play a key role in predicting donation attitudes and intentions. Mediational pathways provide support for interventions to improve donation intentions by addressing specific fears while also improving a donor's belief in his or her ability to manage donation-related fears.

Factors that contribute to blood donation behavior among primary healthcare users: A structural approach.

This study aimed to evaluate the relative contribution of psychosocial variables to donation behavior in a sample of primary healthcare users in a Brazilian municipality. Donor recruitment and retention continue to pose significant challenges to blood collection services worldwide and is especially important among low and middle income countries (LMICs), challenged with higher rates of stigma and low public awareness about donation. A cross-sectional study with randomized stratified sampling of 1055 primary healthcare users was conducted across 12 healthcare facilities in Ribeirão Preto, state of São Paulo. Participants completed measures assessing psychosocial variables, including religiosity, knowledge regarding blood donation process, overall quality of life, blood donation of peers, sociodemographic variables, and the fear of blood, injections, and fainting. The associations between psychosocial variables and donation behaviour was examined using structural equation modelling. Blood donation was more frequent in males and among individuals with higher socioeconomic and educational levels. The structural model indicated associations between blood donation behaviour and fear, knowledge, age, sex, socioeconomic status, and educational level. Fear of blood, injections and vasovagal reactions, and a lack of knowledge of the donation process were revealed as important barriers to the decision to donate blood. In addition, there is evidence that considering the population of primary healthcare users, the women, the youngers, and those with lower socioeconomic status and lower educational level are less likely to donate blood.

40th International Asilomar Chromatin, Chromosomes, and Epigenetics Conference.

The 40th International Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held in the Asilomar Conference Grounds, Pacific Grove, California, USA, on 6-9 December 2018. The organizing committee consisted of established scientists in the fields of chromatin and epigenetics: Sally Pasion and Michael Goldman from the Biology Department, San Francisco State University, California, USA; Philippe Georgel from the Department of Biological Sciences, Marshal University, West Virginia, USA; Juan Ausió from the Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada; and Christopher Eskiw from the Department of Biochemistry, University of Saskatchewan, Saskatchewan, Canada. The meeting had two keynote speakers: Jessica Tyler and Jennifer Mitchell, and it covered topics on transcription, replication and repair, epigenetics, cell differentiation and disease, telomeres, and centromeres and it had two sessions devoted to nuclear and genomic organization. It encompassed the enthusiastic presentations of excellent trainees within the breathtaking natural setting of Pacific Grove.

A search for tiny dragons (Dracunculus medinensis third-stage larvae) in aquatic animals in Chad, Africa.

Dracunculus medinensis, or human Guinea worm (GW), causes a painful and debilitating infection. The global Guinea Worm Eradication Program (GWEP) has successfully reduced human GW cases from 3.5 million in 21 countries in 1986 to only 30 cases in three remaining countries in 2017. Since 2012, an increase in GW infections in domestic dogs, cats and baboons has been reported. Because these infections have not followed classical GW epidemiological patterns resulting from water-borne transmission, it has been hypothesized that transmission occurs via a paratenic host. Thus, we investigated the potential of aquatic animals to serve as paratenic hosts for D. medinensis in Chad, Africa. During three rainy and two dry season trips we detected no GW larvae in 234 fish, two reptiles and two turtles; however, seven GW larvae were recovered from 4 (1.4%) of 276 adult frogs. These data suggest GW infections may occur from ingestion of frogs but the importance of this route is unknown. Additional studies are needed, especially for other possible routes (e.g., ingestion of fish intestines that were recently shown to be a risk). Significantly, 150 years after the life cycle of D. medinensis was described, our data highlights important gaps in the knowledge of GW ecology.

Prediction Errors in Depression: A Quasi-Experimental Analysis.

The overprediction and underprediction of fear, pain, and other constructs have been linked with etiology and maintenance of anxiety disorders. We aimed to extend this research to depression by investigating the overprediction of effort and the underprediction of reward and enjoyment associated with a simple task. Participants with depression (n = 20) and a control group (n = 40) predicted how much effort and reward/enjoyment would be experienced during a short walk around the university. Post-walk, participants reported the actual effort required and the actual experienced reward and enjoyment. Compared to the control group, who demonstrated accurate predictions, depressed individuals significantly overpredicted the required effort associated with the walk even though there were no between-group differences in actual effort required. There was no evidence to suggest that the depressed group underestimated or were inaccurate in their predictions of walk-related reward and enjoyment relative to the control group. Implications for cognitive and behavioral approaches to depression are discussed.

The paradox of moral cleansing: When physical cleansing leads to increased contamination concerns.

BACKGROUND AND OBJECTIVES: Moral threats, including threats to moral self-worth, have been associated with contamination concerns. Paradoxically, although self-cleansing provides temporary relief, it can worsen feelings of contamination. Self-affirmation might be an effective strategy, especially following obsessive type cognitions (e.g., responsibility beliefs) when moral threats are reactivated. METHODS: In Experiment 1, participants recalled an immoral deed and then self-cleansed (using a hand-wipe), completed a control task, or self-affirmed. Contamination concerns were subsequently measured by a washing task. In Experiment 2, the same procedure was used but obsessive-type cognitions were activated by asking participants a series of questions about obsessive beliefs. RESULTS: As expected, relative to the control condition, both self-affirmation and self-cleansing resulted in less subsequent repeated washing behaviour in Experiment 1. In Experiment 2, when the immoral recall was followed by activation of obsessive-type cognitions, self-cleansing led to more guilt and repeated washing than self-affirmation and control. Rather than alleviating feelings of contamination, physical self-cleansing led to more contamination concerns and guilt when in the context of activated obsessive-type cognitions, possibly because it paradoxically makes (moral) cleanliness goals salient. LIMITATIONS: Future research needs to test clinical populations, for whom contamination concerns are all the more central. CONCLUSIONS: This research provides further evidence of the influence of moral threat in contamination concerns, and the limits of moral cleansing. Self-affirmation resulted in less contamination concerns under both a neutral condition and activated obsessive type cognitions.

SPALAX NG: A breakthrough in radioxenon field measurement.

Lessons-learned from 10 years of noble gas stations operation and dedicated R&D allowed the design of a New Generation of station. In order to produce 60m3 air equivalent Xenon samples every 8h, it implements: (i) larger sampler unit for Xenon extraction (2 compressors and 8 nitrogen membranes), (ii) new noble gas adsorbent (Ag@ZSM5), (iii) hardened components and (iv) new high resolution coincidence low background spectrometer (HPGe/PIPSBox). Station expected radioxenon sensitivity is lower than 0.3mBq/m3.

MeCP2 and CTCF: enhancing the cross-talk of silencers.

This paper provides a brief introductory review of the most recent advances in our knowledge about the structural and functional aspects of two transcriptional regulators: MeCP2, a protein whose mutated forms are involved in Rett syndrome; and CTCF, a constitutive transcriptional insulator. This is followed by a description of the PTMs affecting these two proteins and an analysis of their known interacting partners. A special emphasis is placed on the recent studies connecting these two proteins, focusing on the still poorly understood potential structural and functional interactions between the two of them on the chromatin substrate. An overview is provided for some of the currently known genes that are dually regulated by these two proteins. Finally, a model is put forward to account for their possible involvement in their regulation of gene expression.