Subcutaneous rupture of the Achilles tendon and ipsilateral fracture of the medial malleolus

BACKGROUND: Although ankle fractures and an Achilles tendon rupture are relatively frequent in isolation, their association in the same injury is uncommon. CASE PRESENTATION: A 38 year old male tree surgeon fell six meters from a tree, sustaining a subcutaneous rupture of the Achilles tendon and an ipsilateral closed fracture of the medial malleolus. The injuries were diagnosed following clinical examination and imaging. CONCLUSION: This injury combination is infrequent, and management of the Achilles tendon rupture should take into account the necessity not to secondarily displace the fracture of the medial malleollus

The OMERACT Core Domain Set for Clinical Trials of Shoulder Disorders.

OBJECTIVE:To reach consensus on the core domains to be included in a core domain set for clinical trials of shoulder disorders using the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Core Domain Set process. METHODS:At OMERACT 2018, the OMERACT Shoulder Working Group conducted a workshop that presented the OMERACT 2016 preliminary core domain set and its rationale based upon a systematic review of domains measured in shoulder trials and international Delphi sessions involving patients, clinicians, and researchers, as well as a new systematic review of qualitative studies on the experiences of people with shoulder disorders. After discussions in breakout groups, the OMERACT core domain set for clinical trials of shoulder disorders was presented for endorsement by OMERACT 2018 participants. RESULTS:The qualitative review (n = 8) identified all domains included in the preliminary core set. An additional domain, cognitive dysfunction, was also identified, but confidence that this represents a core domain was very low. The core domain set that was endorsed by the OMERACT participants, with 71% agreement, includes 4 "mandatory" trial domains: pain, function, patient global - shoulder, and adverse events including death; and 4 "important but optional" domains: participation (recreation/work), sleep, emotional well-being, and condition-specific pathophysiological manifestations. Cognitive dysfunction was voted out of the core domain set. CONCLUSION:OMERACT 2018 delegates endorsed a core domain set for clinical trials of shoulder disorders. The next step includes identification of a core outcome measurement set that passes the OMERACT 2.1 Filter for measuring each domain

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

FRA2A is a CGG repeat expansion associated with silencing of AFF3

Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship

Loading protocols for European regions of low to moderate seismicity

Existing loading protocols for quasi-static cyclic testing of structures are based on recordings from regions of high seismicity. For regions of low to moderate seismicity they overestimate imposed cumulative damage demands. Since structural capacities are a function of demand, existing loading protocols applied to specimens representative of structures in low to moderate seismicity regions might underestimate structural strength and deformation capacity. To overcome this problem, this paper deals with the development of cyclic loading protocols for European regions of low to moderate seismicity. Cumulative damage demands imposed by a set of 60 ground motion records are evaluated for a wide variety of SDOF systems that reflect the fundamental properties of a large portion of the existing building stock. The ground motions are representative of the seismic hazard level corresponding to a 2% probability of exceedance in 50 years in a European moderate seismicity region. To meet the calculated cumulative damage demands, loading protocols for different structural types and vibration periods are developed. For comparison, cumulative seismic demands are also calculated for existing protocols and a set of records that was used in a previous study on loading protocols for regions of high seismicity. The median cumulative demands for regions of low to moderate seismicity are significantly less than those of existing protocols and records of high seismicity regions. For regions of low to moderate seismicity the new protocols might therefore result in larger strength and deformation capacities and hence in more cost-effective structural configurations or less expensive retrofit measures

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Patients' experience of shoulder disorders: a systematic review of qualitative studies for the OMERACT Shoulder Core Domain Set.

OBJECTIVES:To describe the experiences (including symptoms and perceived impacts on daily living) of people with a shoulder disorder. METHODS:Systematic review of qualitative studies. We searched for eligible qualitative studies indexed in Ovid MEDLINE, Ovid Embase, CINAHL (EBSCO), SportDiscus (EBSCO) and Ovid PsycINFO up until November 2017. Two authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist, used thematic synthesis methods to generate themes describing the experiences reported by participants and assessed the confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. RESULTS:The inclusion criteria were met by eight studies, which included 133 participants (49 females and 84 males) with either rotator cuff disease, adhesive capsulitis, proximal humeral fracture, shoulder instability or unspecified shoulder pain. We generated seven themes to describe what people in the included studies reported experiencing: pain; physical function/activity limitations; participation restriction; sleep disruption; cognitive dysfunction; emotional distress; and other pathophysiological manifestations (other than pain). There were interactions between the themes, with particular experiences impacting on others (e.g. pain leading to reduced activities and sleep disruption). Following grading of the evidence, we considered it likely that most of the review findings were a reasonable representation of the experiences of people with shoulder disorders. CONCLUSION:Patients with shoulder disorders contend with considerable disruption to their life. The experiences described should be considered by researchers seeking to select the most appropriate outcomes to measure in clinical trials and other research studies in people with shoulder disorders

A promoting early presentation intervention increases breast cancer awareness in older women after 2 years: a randomised controlled trial

BACKGROUND: We have developed the Promoting Early Presentation (PEP) Intervention to equip older women with the knowledge, skills, confidence and motivation to present promptly with breast symptoms, and thereby improve survival from breast cancer. The PEP Intervention consists of a 10-min interaction between a radiographer and an older woman, supported by a booklet. Our previous report showed that at 1 year, the PEP intervention increased the proportion who were breast cancer aware compared with usual care.METHODS: We randomised 867 women aged 67-70 years attending for their final routine appointment on the National Health Service Breast Screening Programme to receive the PEP Intervention, a booklet alone or usual care. The primary outcome was breast cancer awareness measured using a validated questionnaire asking about knowledge of breast cancer symptoms, knowledge that the risk of breast cancer increases with age and breast checking behaviour.RESULTS: At 2 years, the PEP Intervention increased the proportion who were breast cancer aware compared with usual care (21 vs 6%; odds ratio 8.1, 95% confidence interval 2.7-25.0).CONCLUSIONS: The uniquely large and sustained effect of the PEP Intervention on breast cancer awareness increases the likelihood that a woman will present promptly should she develop breast cancer symptoms up to many years later. British Journal of Cancer (2011) 105, 18-21. doi: 10.1038/bjc.2011.205 www.bjcancer.com Published online 7 June 2011 (C) 2011 Cancer Research U