2,009 research outputs found

    The descriptive epidemiology of accelerometer-measured physical activity in older adults.

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    BACKGROUND: Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults. METHODS: Physical activity was measured by uniaxial accelerometry in 4,052 UK (49-91 years) and 3459 US older adults (49-85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent 809 counts/minute is used 18.7% of people reached the 30 min/day threshold. By comparison, 2.5% and 9.5% of American older adults accumulated activity at these levels, respectively. CONCLUSION: As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults.This work was supported by programme grants from the Medical Research Council [G9502233; G0401527] and Cancer Research UK [C864/A8257]. A grant from Research into Ageing [262] funded the 3rd health check clinic. KW is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship [FS/12/58/29709], and AJMC, SJG, NJW, and SB are supported by MRC programme grants [MC_UU_12015/3 and MC_UU_12015/4].This is the final version of the article. It was first available from BioMed Central via http://dx.doi.org/10.1186/s12966-015-0316-

    Non-invasive management of peripheral arterial disease.

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    BACKGROUND: Peripheral arterial disease (PAD) is common and symptoms can be debilitating and lethal. Risk management, exercise, radiological and surgical intervention are all valuable therapies, but morbidity and mortality rates from this disease are increasing. Circulatory enhancement can be achieved using simple medical electronic devices, with claims of minimal adverse side effects. The evidence for these is variable, prompting a review of the available literature. METHODS: Embase and Medline were interrogated for full text articles in humans and written in English. Any external medical devices used in the management of peripheral arterial disease were included if they had objective outcome data. RESULTS: Thirty-one papers met inclusion criteria, but protocols were heterogenous. The medical devices reported were intermittent pneumatic compression (IPC), electronic nerve (NMES) or muscle stimulators (EMS), and galvanic electrical dressings. In patients with intermittent claudication, IPC devices increase popliteal artery velocity (49-70 %) and flow (49-84 %). Gastrocnemius EMS increased superficial femoral artery flow by 140 %. Over 4.5-6 months IPC increased intermittent claudication distance (ICD) (97-150 %) and absolute walking distance (AWD) (84-112 %), with an associated increase in quality of life. NMES of the calf increased ICD and AWD by 82 % and 61-150 % at 4 weeks, and 26 % and 34 % at 8 weeks. In patients with critical limb ischaemia IPC reduced rest pain in 40-100 % and was associated with ulcer healing rates of 26 %. IPC had an early limb salvage rate of 58-83 % at 1-3 months, and 58-94 % at 1.5-3.5 years. No studies have reported the use of EMS or NMES in the management of CLI. CONCLUSION: There is evidence to support the use of IPC in the management of claudication and CLI. There is a building body of literature to support the use of electrical stimulators in PAD, but this is low level to date. Devices may be of special benefit to those with limited exercise capacity, and in non-reconstructable critical limb ischaemia. Galvanic stimulation is not recommended

    A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

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    Background: More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5′ and 3′ ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results: The CYP21A2 sequencing analysis showed that the patient was homozygote for the g.655C/A<G mutation and heterozygote for the p.P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g.656C/A<G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p.P30L and the g.655C/A<G splice mutation. Conclusion: We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLA-B15, DR13 haplotype, in a young Italian CAH patient. © 2009 Concolino et al; licensee BioMed Central Ltd

    Reverberation Mapping and the Physics of Active Galactic Nuclei

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    Reverberation-mapping campaigns have revolutionized our understanding of AGN. They have allowed the direct determination of the broad-line region size, enabled mapping of the gas distribution around the central black hole, and are starting to resolve the continuum source structure. This review describes the recent and successful campaigns of the International AGN Watch consortium, outlines the theoretical background of reverberation mapping and the calculation of transfer functions, and addresses the fundamental difficulties of such experiments. It shows that such large-scale experiments have resulted in a ``new BLR'' which is considerably different from the one we knew just ten years ago. We discuss in some detail the more important new results, including the luminosity-size-mass relationship for AGN, and suggest ways to proceed in the near future.Comment: Review article to appear in Astronomical Time Series, Proceedings of the Wise Observatory 25th Ann. Symposium. 24 pages including 7 figure

    DHODH modulates transcriptional elongation in the neural crest and melanoma

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    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

    Melioidosis presenting with mediastinal lymphadenopathy masquerading as malignancy: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Melioidosis, endemic in Thailand and in the Northern Territory of Australia is an emerging infectious disease in India which can present with varied forms. A case of melioidosis, presenting as a rare anterior mediastinal mass which can masquerade as malignancy or tuberculosis, is described here. With treatment, our patient initially showed an increase in the size of mediastinal node and development of new submandibular node.. To the best of our knowledge, this phenomenon has not been documented in the literature and the same is highlighted in this case report. </p> <p>Case Presentation</p> <p>A 43-year-old Asian man with diabetes presented with fever, loss of appetite, weight loss for one month and painful swelling below his left mandible for five days. An examination revealed an enlarged left submandibular lymph node and bilateral axillary lymph nodes. A chest X-ray showed mediastinal widening. Computed tomography of his thorax showed a lobulated heterogeneously enhancing anterior mediastinal mass encasing the superior vena cava suggestive of malignancy. An excision biopsy of the lymph node showed granulomas suggestive of tuberculosis but bone marrow culture and lymph node aspirate culture grew <it>Burkholderia pseudomallei</it>. He was treated with parenteral ceftazidime and amoxicillin-clavulanic acid. During the course of treatment, he developed an enlargement of the submandibular lymph node on the opposite side. It gradually subsided with the continuation of therapy orally with a combination of cotrimoxazole and doxycycline for six months. A repeat computed tomography chest scan showed resolution of the mediastinal mass.</p> <p>Conclusion</p> <p>Melioidosis can present as a mediastinal mass that mimics tuberculosis or malignancy. During the initial phase of treatment of melioidosis, the appearance of new lymph nodes or an increase in the size of the existing lymph nodes does not mean treatment failure. Inexperienced clinicians may consider this as treatment failure and may switch treatment. To the best of our knowledge, this is the first report documenting this phenomenon in melioidosis cases.</p

    Kank Is an EB1 Interacting Protein that Localises to Muscle-Tendon Attachment Sites in Drosophila

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    Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role in the regulation of microtubule plus ends. It directly binds to microtubule plus ends and recruits proteins which regulate microtubule dynamics and behaviour. We report the identification of Kank, the sole Drosophila orthologue of human Kank proteins, as an EB1 interactor that predominantly localises to embryonic attachment sites between muscle and tendon cells. Human Kank1 was identified as a tumour suppressor and has documented roles in actin regulation and cell polarity in cultured mammalian cells. We found that Drosophila Kank binds EB1 directly and this interaction is essential for Kank localisation to microtubule plus ends in cultured cells. Kank protein is expressed throughout fly development and increases during embryogenesis. In late embryos, it accumulates to sites of attachment between muscle and epidermal cells. A kank deletion mutant was generated. We found that the mutant is viable and fertile without noticeable defects. Further analysis showed that Kank is dispensable for muscle function in larvae. This is in sharp contrast to C. elegans in which the Kank orthologue VAB-19 is required for development by stabilising attachment structures between muscle and epidermal cells

    Laetoli's lost tracks: 3D generated mean shape and missing footprints.

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    The Laetoli site (Tanzania) contains the oldest known hominin footprints, and their interpretation remains open to debate, despite over 35 years of research. The two hominin trackways present are parallel to one another, one of which is a composite formed by at least two individuals walking in single file. Most researchers have focused on the single, clearly discernible G1 trackway while the G2/3 trackway has been largely dismissed due to its composite nature. Here we report the use of a new technique that allows us to decouple the G2 and G3 tracks for the first time. In so doing we are able to quantify the mean footprint topology of the G3 trackway and render it useable for subsequent data analyses. By restoring the effectively 'lost' G3 track, we have doubled the available data on some of the rarest traces directly associated with our Pliocene ancestors

    Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

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    This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community
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