Search results
Found 5948 matches for
Changes in the way that neurons communicate with each other affect our ability to move between sleep and wake states.
Recruitment, Retention, and Training of Citizen Scientists in Translational Medicine Research: A Citizen Science Initiative on Non-Alcoholic Fatty Liver Disease.
Citizen science is a participatory science approach in which members of the public (citizens) collaborate with scientists and professional researchers and become involved in research and innovation activities, resulting in the co-creation of scientific knowledge and innovation. Citizen science has been widely applied in research, particularly in the social sciences, environmental sciences, information and communication technologies, and public health. However, the application of this approach in clinical sciences, particularly in translational medicine research, is still nascent. This exploratory study involved members of the public (citizen scientists) in a translational medicine experiment on non-alcoholic fatty liver disease that incorporated a lifestyle and weight-loss intervention. The aim of this paper is to report successful methods and approaches for the recruitment, retention, and training of citizen scientists. For the citizen scientists' recruitment, online calls placed on the websites of our research project and biomedical research center and targeted emails were the most helpful. Of the 14 members of the public who expressed interest in our study, six were recruited as citizen scientists. Citizen scientists were mostly female (n = 5, 83%), white (n = 3, 50%), over 50 years of age (n = 4, 67%), educated to postgraduate level (n = 5, 83%), and either retired or not in employment (n = 5, 83%). The retention rate was 83% (n = 5), and the dropout rate was 17% (n = 1). We arranged instructor-led interactive online training sessions (an hour-long one-on-one session and two-hour group sessions). Research skills training covered ethics in research and qualitative and quantitative data analysis. Citizen scientists were given several incentives, such as reimbursement of travel and care costs, selection as citizen scientists of the month, publications of their blogs and perspective articles, and co-authorship and acknowledgement in papers and project deliverables. To conclude, members of the public (particularly middle-aged white women with postgraduate education) are interested in becoming citizen scientists in translational medicine research. Their retention rate is higher, and they can contribute to different research activities. However, they need training to develop their research skills and expertise. The training should be simple, comprehensive, and flexible to accommodate the schedules of individual citizen scientists. They deserve incentives as they work on a voluntary basis.
Interstitial pneumonitis following mitozantrone, chlorambucil and prednisolone (MCP) chemotherapy.
We describe two cases of interstitial lung disease in patients with non-Hodgkin's lymphoma who were treated with combination chemotherapy including mitozantrone. In both we had radiological and histological evidence of interstitial lung disease, with patterns of organizing pneumonia and hypersensitivity without a clear aetiological agent. Clinical resolution occurred on withdrawal of chemotherapy. One patient required a course of corticosteroid treatment. To date, both patients are well and in remission, and there has been no recurrence of their respiratory disease. We postulate that these observations are hitherto undescribed pulmonary abnormalities secondary to mitozantrone therapy.
Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets.
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity. METHODS: We analysed 2,941 plasma proteins in 43,978 European participants from UK Biobank. We performed genome-wide association study (GWAS) for all MASLD-associated proteins and created the largest MASLD GWAS (109,885 cases/1,014,923 controls). We performed Mendelian Randomization (MR) and integrated proteins and their encoding genes in MASLD ranges to identify candidate causal proteins. We then validated them through independent replication, exome sequencing, liver imaging, bulk and single-cell gene expression, liver biopsies, pathway, and phenome-wide data. We explored the role of obesity by MR and multivariable MR across proteins, body mass index, and MASLD. RESULTS: We found 929 proteins associated with MASLD, reported five novel genetic loci associated with MASLD, and identified 17 candidate MASLD protein targets. We identified four novel targets for MASLD (CD33, GRHPR, HMOX2, and SCG3), provided protein evidence supporting roles of AHCY, FCGR2B, ORM1, and RBKS in MASLD, and validated nine previously known targets. We found that CD33, FCGR2B, ORM1, RBKS, and SCG3 mediated the association of obesity and MASLD, and HMOX2, ORM1, and RBKS had effect on MASLD independent of obesity. CONCLUSIONS: This study identified new protein targets in the causal pathway of MASLD, providing new insights into the multi-omics architecture and pathophysiology of MASLD. These findings advise further therapeutic interventions for MASLD.
Effects of cognitive behavioural therapy and bright light therapy for insomnia in youths with eveningness: study protocol for a randomised controlled trial.
BACKGROUND: Insomnia and eveningness are common and often comorbid conditions in youths. While cognitive behavioural therapy for insomnia (CBT-I) has been suggested as a promising intervention, it remains unclear whether it is sufficient to also address circadian issues in youths. In addition, despite that light has been shown to be effective in phase-shifting one's circadian rhythm, there has been limited data on the effects of bright light therapy and its combination with CBT-I on sleep and circadian outcomes in youths. The current protocol outlines a randomised controlled trial that examines the efficacy of CBT-I and CBT-I plus bright light therapy (BLT) in reducing insomnia severity, improving mood symptoms and daytime functioning (e.g. sleepiness, fatigue, cognitive function), and improving subjective and objective sleep and circadian measures compared to a waitlist control group. METHODS: We will carry out a randomised controlled trial (RCT) with 150 youths aged 12-24 who meet the criteria of insomnia and eveningness. Participants will be randomised into one of three groups: CBT-I with bright light therapy, CBT-I with placebo light, and waitlist control. Six sessions of CBT-I will be delivered in a group format, while participants will be currently asked to use a portable light device for 30 min daily immediately after awakening throughout the intervention period for bright light therapy. The CBT-I with light therapy group will receive bright constant green light (506 lx) while the CBT-I with placebo light group will receive the modified light device with the LEDs emitting less than 10 lx. All participants will be assessed at baseline and post-treatment, while the two active treatment groups will be additionally followed up at 1 month and 6 months post-intervention. The primary outcome will be insomnia severity, as measured by the Insomnia Severity Index. Secondary outcomes include self-reported mood, circadian, daytime functioning, and quality of life measures, as well as sleep parameters derived from actigraphy and sleep diary and neurocognitive assessments. Objective measures of the circadian phase using dim-light melatonin onset assessment and sleep parameters using polysomnography will also be included as the secondary outcomes. DISCUSSION: This study will be the first RCT to directly compare the effects of CBT-I and BLT in youths with insomnia and eveningness. Findings from the study will provide evidence to inform the clinical management of insomnia problems and eveningness in youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT04256915. Registered on 5 February 2020.
The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets.
Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca2+ on intrinsic α-cell glucagon secretion. Blocking isradipine-sensitive L-type voltage-gated Ca2+ (Cav) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca2+ oscillations or low-glucose-stimulated glucagon secretion. In contrast, depleting ER Ca2+ with cyclopiazonic acid or blocking ER Ca2+-releasing ryanodine receptors abolished α-cell glucose sensitivity and low-glucose-stimulated glucagon secretion. ER Ca2+ mobilization in α-cells is regulated by intracellular ATP and likely to be coupled to Ca2+ influx through P/Q-type Cav channels. ω-Agatoxin IVA blocked α-cell ER Ca2+ release and cell exocytosis, but had no additive effect on glucagon secretion when combined with ryanodine. We conclude that glucose regulates glucagon secretion through the control of ER Ca2+ mobilization, a mechanism that can be independent of α-cell electrical activity.