511 research outputs found

    Early transverse tubule development begins in utero in the sheep heart.

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    Published onlineJournal ArticleThis is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.The ventricular cardiomyocytes of adult mammals contain invaginations of the plasma membrane known as transverse (t)-tubules. These regular structures are essential for the synchronisation of excitation-contraction (EC) coupling throughout the cell, which is a vital process for cardiac function. T-tubules form a close association with the sarcoplasmic reticulum (SR) to form junctions, where several key proteins involved in EC coupling are localised, including the SR calcium release channels-the ryanodine receptors (RyR). The lipophilic SR protein junctophilin-2 (JPH2) has been implicated in the development of both the junctions and t-tubules. Several studies have identified that t-tubules develop only postnatally in rodents, while historical electron microscopy data indicate that this is not the case in larger mammals, including humans. We have performed, to our knowledge, the first fluorescent, target-specific study to characterise t-tubule development in the large mammalian fetal heart, focussing on the sheep. T-tubules were present in fetal sheep hearts from 114 days gestation (with term being 145 days), with occurrence progressively increasing with gestational age, and further maturation after birth. This was accompanied by an increasing intracellular localisation of JPH2, which progressively increased its association with RyR within the cardiomyocytes as they undergo hypertrophy. These findings indicate that large mammalian hearts exhibit a significantly different temporal pattern of development compared to that of the rodent. Our findings have potential implications for human cardiac development, including the future investigation of congenital heart disease.This research was supported by a Health Research Council of New Zealand grant (#12/240) awarded to CS. We wish to thank Prof Laura Bennet, Dr Joanne Davidson and the Fetal Physiology & Neuroscience group, Department of Physiology, University of Auckland for supplying the tissue used in this study, with original projects supported by Health Research Council of New Zealand research grants (#14/216 and #12/613)

    Bone marrow transplantation in AML, and socioeconomic class: a UK population-based cohort study

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    <p>Abstract</p> <p>Background</p> <p>We have previously shown that in the UK mortality in people with Acute Myeloid Leukaemia (AML) was nearly 50% greater among the most socio-economically deprived. The aim of this study was to determine whether AML patients from lower socioeconomic classes had a lower chance of receiving a bone marrow transplant.</p> <p>Methods</p> <p>Using Hospital Episode Statistics (HES) data, we identified all incident cases of AML admitted to UK hospitals between 1998 and 2007. We calculated the number of bone marrow transplantations undertaken in AML patients, stratifying our results by gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity. We used logistic regression to calculate odds ratios for bone marrow transplantation, adjusting for gender, age at diagnosis, year of diagnosis, degree of socioeconomic deprivation and co-morbidity score.</p> <p>Results</p> <p>We identified a total of 23 910 incident cases of AML over this 10-year time period, of whom 1 140 (4.8%) underwent BMT. Bone marrow transplantation declined with increasing socioeconomic deprivation (p for trend < 0.001) such that people in the most deprived socioeconomic quintile were 40% less likely to have a transplant than those in the most advantaged group (Odds Ratio 0.60, 95% confidence interval 0.49, 0.73), even after adjusting for gender, age at diagnosis, year of diagnosis and co-morbidity.</p> <p>Conclusion</p> <p>This large cohort study demonstrates that AML patients from lower socioeconomic classes are less likely to undergo bone marrow transplantation than their better off counter-parts.</p

    Prolonged venous bleeding due to traditional treatment with leech bite: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>The medicinal leech, <it>Hirudo medicinalis</it>, has been used in the treatment of many diseases for thousands of years. In Turkey, it is used most commonly in the management of venous diseases of lower extremities.</p> <p>Case presentation</p> <p>A 25-year-old Turkish woman presented to our emergency room with bleeding from her left leg. She had been treated for varicose veins in her lower extremities with leeches about 24 hours before admission to the emergency room. The bleeding was controlled by applying pressure with sterile gauze upon the wound, and she was discharged. She returned after four hours having started bleeding again. Hemostasis was achieved by vein ligation under local anesthesia.</p> <p>Conclusions</p> <p>Leech bite should be evaluated as a special injury. Prolonged bleeding can be seen after leech bites. In such cases, hemostasis either with local pressure or ligation of the bleeding vessel is mandatory.</p

    Effect of Environmental Tobacco Smoke on Levels of Urinary Hormone Markers

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    Our recent study showed a dose–response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E(1)C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E(1)C levels in a ±10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E(1)C levels (β= –0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (β= –0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E(1)C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E(1)C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects

    Algorithms in the Ultra-Wide Word Model

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    The effective use of parallel computing resources to speed up algorithms in current multi-core parallel architectures remains a difficult challenge, with ease of programming playing a key role in the eventual success of various parallel architectures. In this paper we consider an alternative view of parallelism in the form of an ultra-wide word processor. We introduce the Ultra-Wide Word architecture and model, an extension of the word-RAM model that allows for constant time operations on thousands of bits in parallel. Word parallelism as exploited by the word-RAM model does not suffer from the more difficult aspects of parallel programming, namely synchronization and concurrency. For the standard word-RAM algorithms, the speedups obtained are moderate, as they are limited by the word size. We argue that a large class of word-RAM algorithms can be implemented in the Ultra-Wide Word model, obtaining speedups comparable to multi-threaded computations while keeping the simplicity of programming of the sequential RAM model. We show that this is the case by describing implementations of Ultra-Wide Word algorithms for dynamic programming and string searching. In addition, we show that the Ultra-Wide Word model can be used to implement a nonstandard memory architecture, which enables the sidestepping of lower bounds of important data structure problems such as priority queues and dynamic prefix sums. While similar ideas about operating on large words have been mentioned before in the context of multimedia processors [Thorup 2003], it is only recently that an architecture like the one we propose has become feasible and that details can be worked out.Comment: 28 pages, 5 figures; minor change

    Evaluation of the effectiveness of music therapy in improving the quality of life of palliative care patients: a randomised controlled pilot and feasibility study.

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    BACKGROUND: Music therapy is frequently used as a palliative therapy. In consonance with the goals of palliative care, the primary aim of music therapy is to improve people's quality of life by addressing their psychological needs and facilitating communication. To date, primarily because of a paucity of robust research, the evidence for music therapy's effectiveness on patient reported outcomes is positive but weak. This pilot and feasibility study will test procedures, outcomes and validated tools; estimate recruitment and attrition rates; and calculate the sample size required for a phase III randomised trial to evaluate the effectiveness of music therapy in improving the quality of life of palliative care patients. METHODS: A pilot randomised controlled trial supplemented with qualitative methods. The quantitative data collection will involve recruitment of >52 patients from an inpatient Marie Curie hospice setting over a 12-month period. Eligibility criteria include all patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 03- indicating they are medically fit to engage with music therapy and an Abbreviated Mental Test (AMT) score of ≥7 indicating they are capable of providing meaningful informed consent and accurate responses to outcome measures. Baseline data collection will include the McGill Quality of Life Questionnaire (MQOL); medical and socio-demographic data will be undertaken before randomisation to an intervention or control group. Participants in the intervention arm will be offered two 30-45 min sessions of music therapy per week for three consecutive weeks, in addition to care as usual. Participants in the control arm will receive care as usual. Follow-up measures will be administered in 1, 3 and 5 weeks. Qualitative data collection will involve focus group and individual interviews with HCPs and carers. DISCUSSION: This study will ensure a firm methodological grounding for the development of a robust phase III randomised trial of music therapy for improving quality of life in palliative care patients. By undertaking the pilot and feasibility trial under normal clinical conditions in a hospice setting, the trial will result in reliable procedures to overcome some of the difficulties in designing music therapy RCTs for palliative care settings. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02791048

    Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

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    This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
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