Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To ...identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To prepare medical students for a rapidly changing healthcare landscape, where new means of communication emerge, innovative teaching methods are needed. We developed a project-based learning course ...in which medical students design audiovisual patient information in collaboration with patients and with students in Communication and Information Sciences (CIS). We studied what learning mechanisms are triggered in medical students by elements of a project-based-learning course.
In this qualitative study, twelve sixth year medical students that participated in the course were individually interviewed. Data were analyzed according to the principles of qualitative template analysis.
We identified four learning mechanisms: Challenging assumptions about patients’ information needs; Becoming aware of the origin of patients’ information needs; Taking a patient’s perspective; Analyzing language to adapt to patients’ needs. These learning mechanisms were activated by making a knowledge clip, collaborating with patients, and collaborating with CIS students.
Collaborating with patients helped students to recognize and understand patients’ perspectives. Working on a tangible product in partnership with patients and CIS students, triggered students to apply their understanding in conveying information back to patients.
Based on our findings we encourage educators to involve patients as collaborators in authentic assignments for students so they can apply what they learned from taking patients’ perspectives.
•We describe a project-based learning course to develop patient information.•Medical students cooperated with a patient and a communication student.•Communication students gave advice on communication and offered a layman perspective.•Collaborating with patients helped students to understand patients’ perspectives.•Cocreating patient information enabled students to apply this understanding.
Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which ...is unknown. In order to elucidate the underlying mechanisms of weight loss in HD, we studied its relation to other disease characteristics including motor, cognitive, and behavioral disturbances and CAG repeat number.
In 517 patients with early stage HD, we applied mixed-effects model analyses to correlate weight changes over 3 years to CAG repeat number and various components of the Unified Huntington's Disease Rating Scale (UHDRS). We also assessed the relation between CAG repeat number and body weight and caloric intake in the R6/2 mouse model of HD.
In patients with HD, mean body mass index decreased with -0.15 units per year (p < 0.001). However, no single UHDRS component, including motor, cognitive, and behavioral scores, was independently associated with the rate of weight loss. Patients with HD with a higher CAG repeat number had a faster rate of weight loss. Similarly, R6/2 mice with a larger CAG repeat length had a lower body weight, whereas caloric intake increased with larger CAG repeat length.
Weight loss in Huntington disease (HD) is directly linked to CAG repeat length and is likely to result from a hypermetabolic state. Other signs and symptoms of HD are unlikely to contribute to weight loss in early disease stages. Elucidation of the responsible mechanisms could lead to effective energy-based therapeutics.
Objectives
To explore the prevalence of dysphagia and fear of choking in patients with Huntington’s disease (HD) as well as preventive measures, both those applied and those not included in managing ...dysphagia. Also, to investigate related problems encountered by their formal and informal caregivers.
Design
A multi-center observational cross-sectional study
Setting and Participants
158 HD patients, recruited from six Dutch nursing homes specialized in HD, and their formal and informal caregivers
Measurements
Patients were assessed by means of questionnaires enquiring about dysphagia, fear of choking and measures to manage dysphagia. Also, questionnaires were administered about awareness of dysphagia symptoms, cognition and anxiety. Because we expected individuals with greater care dependency to have a higher severity of dysphagia, we distinguished between a care-independent and a care-dependent group of HD patients.
Results
In the total group, 90.5% of HD patients had one or more dysphagia symptoms. The prevalence of FoC in HD patients and the formal and informal caregivers’ fears about choking in HD patients was 45.7%, 19.0% and 59.5%, respectively, for care-independent patients and 58.7%, 50.1% and 77.5% for care-dependent patients. The score on the Huntington’s Disease Dysphagia Scale was a predictor for fear of FoC in care-independent patients. Speech-language therapy, supervision during eating and drinking and adaptation of food and drink consistency were the most frequently applied measures to manage dysphagia, a combination was used in most HD patients.
Conclusions
In HD patients, the prevalence of dysphagia is high and fear of choking is common among both patients and caregivers. A more severe degree of dysphagia is a predictor of FoC in care-independent HD patients. A combination of measures was used to manage dysphagia in most HD patients.
Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the ...Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy.
A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded.
Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes.
Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study.
The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington’s disease (HD) and their relationship with cognitive and general ...functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (
n
= 891), hypokinetic-rigid (
n
= 916), or mixed-motor (
n
= 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles.
Rotator cuff tears are common, especially in the fifth and sixth decades of life, but can also occur in the competitive athlete. Genetic differences may contribute to overall injury risk. Identifying ...genetic loci associated with rotator cuff injury could shed light on the etiology of this injury. We performed a genome-wide association screen using publically available data from the Research Program in Genes, Environment and Health including 8,357 cases of rotator cuff injury and 94,622 controls. We found rs71404070 to show a genome-wide significant association with rotator cuff injury with p = 2.31x10-8 and an odds ratio of 1.25 per allele. This SNP is located next to cadherin8, which encodes a protein involved in cell adhesion. We also attempted to validate previous gene association studies that had reported a total of 18 SNPs showing a significant association with rotator cuff injury. However, none of the 18 SNPs were validated in our dataset. rs71404070 may be informative in explaining why some individuals are more susceptible to rotator cuff injury than others.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There has been an increasing focus on determining the psychological mechanisms underlying the broad effects of mindfulness on psychological health. Mindfulness has been posited to be related to the ...construct of reperceiving or decentering, defined as a shift in perspective associated with decreased attachment to one’s thoughts and emotions. Decentering is proposed to be a meta-mechanism that mobilizes four psychological mechanisms (cognitive flexibility, values clarification, self-regulation, and exposure), which in turn are associated with positive health outcomes. Despite preliminary support for this model, extant studies testing this model have not examined distinct facets of mindfulness. The present study used a multidimensional measure of mindfulness to examine whether this model could account for the associations between five facets of mindfulness and psychological symptoms (depressive symptoms, stress, anxiety symptoms, alcohol-related problems) in a sample of college students (
N
= 944). Our findings partially support this model. We found significant double-mediated associations in the expected directions for all outcomes (stress, anxiety symptoms, and depressive symptoms) except alcohol-related problems, and for each of the facets of mindfulness except observing. However, decentering and the specific mechanisms did not fully mediate the associations among mindfulness facets and psychological health outcomes. Experimental and ecological momentary assessment designs are needed to understand the psychological processes that account for the beneficial effects of mindfulness.
Objective: Craving predicts smoking, yet existing interventions may not adequately target regulation of craving. We evaluated two versions of regulation of craving-training (ROC-T), a computerized ...intervention with intensive practice of strategies when exposed to smoking-related images. Method: Ninety-two nicotine-dependent daily smokers were randomized to mindfulness-based therapy (MBT) ROC-T focusing on mindful acceptance, and cognitive behavioral therapy (CBT) ROC-T focusing on reappraisal or no intervention control. The ROC task was administered pre- and postintervention to assess changes in cue-induced craving and mindfulness- and reappraisal-based regulation of craving. Results: MBT and CBT-versus control-showed significantly greater reductions in smoking during the intervention phase (baseline to Week 4), corresponding to large (d = −1.08, 95% CI −1.64, −0.52) and medium-to-large effect sizes (d = −0.69, 95% CI −1.22, −0.15), respectively. During follow-up (Week 4-16), CBT showed significant increases in smoking, whereas MBT and control did not. For the entire study (baseline to Week 16), MBT showed significantly greater reductions in smoking compared to control (d = −1.6, 95% CI −2.56, −0.66) but CBT was not significantly different than control (d = −0.82, 95% CI −1.77, 0.13). There were no effects on smoking when directly comparing MBT and CBT. Quit rates were low across the sample, with no difference among conditions. MBT and CBT-versus control-significantly reduced cue-induced craving. CBT (but not MBT)-versus control-significantly improved reappraisal-based regulation of craving. Both MBT and CBT-versus control-significantly improved mindfulness-based regulation of craving. Conclusions: MBT- and CBT-ROC-T may reduce cue-induced craving and smoking, and MBT may be more durable than CBT.
Public Health Significance Statement
Innovative behavioral interventions for cigarette smoking are needed to reduce relapse rates. We evaluated brief, computerized, mechanism-focused interventions targeting craving, a core mechanism underlying smoking. Findings are promising and suggest that such interventions may play an important role in improving smoking reduction treatment outcomes.
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