Using hypnotic suggestion in the rehabilitation of working memory capacity after acquired brain injury: study protocol for a randomized controlled trial.

OBJECTIVES: Establishment of effective evidence-based interventions in rehabilitation of working memory (WM) deficits after acquired brain injury (ABI) is sorely needed. Despite robust evidence for the efficiency of clinical hypnosis in a wide range of clinical conditions, and improved understanding of mechanisms underlying its effects, the potential of clinical hypnosis in cognitive rehabilitation is underexplored. A recent study has shown large effects of hypnotic suggestion on WM capacity following ABI. This randomized controlled trial aims to evaluate and explore the replicability of these findings and examine the generalization of treatment effects. The study will also explore possible mechanisms of change. METHODS: Ninety patients will be recruited from the Sunnaas Rehabilitation Hospital. Inclusion criteria are nonprogressive ABI, minimum 12-month post-injury, ongoing WM deficits, and age between 18 and 67 years. Patients will be randomized to either (a) an intervention group receiving four weekly 1-h sessions with induction and hypnosis, (b) an active control group receiving four weekly 1-h sessions of induction and mindfulness, or (c) a passive control group without intervention. The targeted procedure consists of suggestions about enhancing WM functions, for example through the instantiation of preinjury WM capacity in the present using age regression or through visualizations of brain plasticity. The non-targeted suggestions contain no explicit mention of ABI- or WM-related abilities. Each participant will be assessed at baseline, immediately after intervention, and 6 months after baseline. The primary outcome is the WM index from WAIS-IV and self- and informant-reported WM subscale from BRIEF-A, a questionnaire exploring executive functioning in everyday life. Secondary outcomes include a cognitive composite score derived from tests measuring processing speed, executive functions, learning capacity and memory, and self-reported measures of emotional distress, quality of life, and community integration. Exploratory measures include self-rated ABI and WM-related self-efficacy. DISCUSSION: Rehabilitation of impaired WM after ABI has hitherto yielded limited transfer effects beyond the training material, i.e., improvement effects on everyday WM capacity, and clinical trials of new interventions are thus warranted. Long-standing empirical evidence demonstrates that hypnosis is an effective therapeutic technique in a wide range of conditions, and recent exploratory research has suggested a high efficacy of hypnosis in improving WM capacity in patients with ABI. However, these extraordinary findings need replication in studies applying scientifically rigorous designs. If successful, our ambition is to provide recommendations and materials to implement hypnotic suggestion as an adjunct treatment following ABI. Study findings may inform future studies exploring the use of clinical hypnosis in other areas of rehabilitation, such as mild TBI, and in other neurological conditions where WM deficit is prominent. TRIAL REGISTRATION: ClinicalTrials.gov NCT05287542. Registered on March 2022 PROTOCOL VERSION: Protocol version 2.0, December 2023.

Oral intake of mesoporous silica is safe and well tolerated in male humans.

BACKGROUND: Precisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated. OBJECTIVE: The aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans. DESIGN: This single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2). RESULTS: All participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred. CONCLUSION: Mesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns.

Red clover (Trifolium pratense L.) draft genome provides a platform for trait improvement.

Red clover (Trifolium pratense L.) is a globally significant forage legume in pastoral livestock farming systems. It is an attractive component of grassland farming, because of its high yield and protein content, nutritional value and ability to fix atmospheric nitrogen. Enhancing its role further in sustainable agriculture requires genetic improvement of persistency, disease resistance, and tolerance to grazing. To help address these challenges, we have assembled a chromosome-scale reference genome for red clover. We observed large blocks of conserved synteny with Medicago truncatula and estimated that the two species diverged ~23 million years ago. Among the 40,868 annotated genes, we identified gene clusters involved in biochemical pathways of importance for forage quality and livestock nutrition. Genotyping by sequencing of a synthetic population of 86 genotypes show that the number of markers required for genomics-based breeding approaches is tractable, making red clover a suitable candidate for association studies and genomic selection.

Influence of rimonabant treatment on peripheral blood mononuclear cells; flow cytometry analysis and gene expression profiling.

The cannabinoid receptor type 1 (CB1) antagonist rimonabant has been used as treatment for obesity. In addition, anti-proliferative effects on mitogen-activated leukocytes have been demonstrated in vitro. We have previously shown that rimonabant (SR141716A) induces cell death in ex vivo isolated malignant lymphomas with high expression of CB1 receptors. Since CB1 targeting may be part of a future lymphoma therapy, it was of interest to investigate possible effects on peripheral blood mononuclear cells (PBMC) in patients treated with rimonabant. We therefore evaluated leukocyte subsets by 6 color flow cytometry in eight patients before and at treatment with rimonabant for 4 weeks. Whole-transcript gene expression profiling in PBMC before and at 4 weeks of rimonabant treatment was done using Affymetrix Human Gene 1.0 ST Arrays. Our data show no significant changes of monocytes, B cells, total T cells or T cell subsets in PBMC during treatment with rimonabant. There was a small but significant increase in CD3-, CD16+ and/or CD56+ cells after rimonabant therapy. Gene expression analysis detected significant changes in expression of genes associated with innate immunity, cell death and metabolism. The present study shows that normal monocytes and leukocyte subsets in blood remain rather constant during rimonabant treatment. This is in contrast to the induction of cell death previously observed in CB1 expressing lymphoma cells in response to treatment with rimonabant in vitro. These differential effects observed on normal and malignant lymphoid cells warrant investigation of CB1 targeting as a potential lymphoma treatment.

The change in eating behaviors in a Web-based weight loss program: a longitudinal analysis of study completers.

BACKGROUND: Eating behaviors are essential components in weight loss programs, but limited research has explored eating behaviors in Web-based weight loss programs. OBJECTIVES: The aim was to evaluate an interactive Web-based weight loss program on eating behaviors using the 18-item Three-Factor Eating Questionnaire Revised (TFEQ-R18) which measures uncontrolled eating, emotional eating, and cognitive restrained eating. Our Web-based weight loss program is comprised of information about healthy lifestyle choices, weekly chats with experts, social networking features, databases for recipe searches, and features allowing members to self-report and track their weight, physical activity, and dietary intake on the website. METHODS: On registering for the weight loss program, 23,333 members agreed to take part in the research study. The participants were then asked to complete the TFEQ-R18 questionnaire at baseline and after 3 and 6 months of participation. All data collection was conducted online, with no face-to-face contact. To study changes in TFEQ-R18 eating behaviors we restricted our study to those members who completed all 3 TFEQ-R18 questionnaires. These participants were defined as "completers" and the remaining as "noncompleters." The relationships between sex, change in eating behaviors, and total weight loss were studied using repeated measures ANOVA and Pearson correlation coefficient. RESULTS: In total, 22,800 individuals participated (females: 19,065/22,800, 83.62%; mean age 39.6, SD 11.4 years; BMI 29.0 kg/m(2); males: 3735/22,800, 16.38%; mean age 43.2, SD 11.7 years; BMI 30.8 kg/m(2)). Noncompleters (n=22,180) were younger and reported a lower score of uncontrolled eating and a higher score of cognitive restrained eating. Over time, completers (n=620) decreased their uncontrolled eating score (from 56.3 to 32.0; P<.001) and increased their cognitive restrained eating (from 50.6 to 62.9; P<.001). Males decreased their emotional eating (from 57.2 to 35.9; P<.001), but no significant change was found among females. The baseline cognitive restrained eating score was significantly and positively associated with weight loss for completers in both men (P=.02) and women (P=.002). CONCLUSIONS: To our knowledge, this is the largest TFEQ sample that has been documented. This Web-based weight loss intervention suggests that eating behaviors (cognitive restrained eating, uncontrolled eating, and emotional eating) measured by TFEQ-R18 were significantly changed during 6 months of participation. Our findings indicate differences in eating behaviors with respect to sex, but should be interpreted with caution because attrition was high.