272 research outputs found

    Rapid phase adjustment of melatonin and core body temperature rhythms following a 6-h advance of the light/dark cycle in the horse

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    <p>Abstract</p> <p>Background</p> <p>Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related circadian disruption is presently unknown in this species. We investigated the rates of re-entrainment of serum melatonin and core body temperature (BT) rhythms following an abrupt 6-h phase advance of the LD cycle in the horse.</p> <p>Methods</p> <p>Six healthy, 2 yr old mares entrained to a 12 h light/12 h dark (LD 12:12) natural photoperiod were housed in a light-proofed barn under a lighting schedule that mimicked the external LD cycle. Following baseline sampling on Day 0, an advance shift of the LD cycle was accomplished by ending the subsequent dark period 6 h early. Blood sampling for serum melatonin analysis and BT readings were taken at 3-h intervals for 24 h on alternate days for 11 days. Disturbances to the subsequent melatonin and BT 24-h rhythms were assessed using repeated measures ANOVA and analysis of Cosine curve fitting parameters.</p> <p>Results</p> <p>We demonstrate that the equine melatonin rhythm re-entrains rapidly to a 6-h phase advance of an LD12:12 photocycle. The phase shift in melatonin was fully complete on the first day of the new schedule and rhythm phase and waveform were stable thereafter. In comparison, the advance in the BT rhythm was achieved by the third day, however BT rhythm waveform, especially its mesor, was altered for many days following the LD shift.</p> <p>Conclusion</p> <p>Aside from the temperature rhythm disruption, rapid resynchronization of the melatonin rhythm suggests that the central circadian pacemaker of the horse may possess a particularly robust entrainment response. The consequences for athletic performance remain unknown.</p

    Idiopathic pulmonary fibrosis and p-ANCA positivity predating manifestations of systemic vasculitis

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    The occurrence of perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA) in pulmonary fibrosis has been reported in a number of small studies, however, the appearance of p-ANCA in already established idiopathic pulmonary fibrosis (IPF), predating the manifestations of vasculitis has not been widely appreciated. We report 2 cases with radiographic evidence of established IPF where p-ANCA was negative at the time of diagnosis and became positive during the course of the disease, for a variable period of time, prior to the subsequent development of systemic vasculitis. Our cases suggest a possible rationale for serial p-ANCA measurements in patients with pulmonary fibrosis even in the absence of features suggestive of vasculitis. Furthermore, the required frequency of ANCA measurement in the absence of clinical features of vasculitis is unknown. Larger studies with repetitive p-ANCA measurement in tandem with ongoing clinical assessment for vasculitis are required to assess the prevalence of ANCA and to confirm our observation

    An assessment of multimodal imaging of subsurface text in mummy cartonnage using surrogate papyrus phantoms

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    Ancient Egyptian mummies were often covered with an outer casing, panels and masks made from cartonnage: a lightweight material made from linen, plaster, and recycled papyrus held together with adhesive. Egyptologists, papyrologists, and historians aim to recover and read extant text on the papyrus contained within cartonnage layers, but some methods, such as dissolving mummy casings, are destructive. The use of an advanced range of different imaging modalities was investigated to test the feasibility of non-destructive approaches applied to multi-layered papyrus found in ancient Egyptian mummy cartonnage. Eight different techniques were compared by imaging four synthetic phantoms designed to provide robust, well-understood, yet relevant sample standards using modern papyrus and replica inks. The techniques include optical (multispectral imaging with reflection and transillumination, and optical coherence tomography), X-ray (X-ray fluorescence imaging, X-ray fluorescence spectroscopy, X-ray micro computed tomography and phase contrast X-ray) and terahertz-based approaches. Optical imaging techniques were able to detect inks on all four phantoms, but were unable to significantly penetrate papyrus. X-ray-based techniques were sensitive to iron-based inks with excellent penetration but were not able to detect carbon-based inks. However, using terahertz imaging, it was possible to detect carbon-based inks with good penetration but with less sensitivity to iron-based inks. The phantoms allowed reliable and repeatable tests to be made at multiple sites on three continents. The tests demonstrated that each imaging modality needs to be optimised for this particular application: it is, in general, not sufficient to repurpose an existing device without modification. Furthermore, it is likely that no single imaging technique will to be able to robustly detect and enable the reading of text within ancient Egyptian mummy cartonnage. However, by carefully selecting, optimising and combining techniques, text contained within these fragile and rare artefacts may eventually be open to non-destructive imaging, identification, and interpretation

    A Systematic Evaluation of Factors Associated With Nocturia—The Population-based FINNO Study

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    In a case-control study with prevalence sampling, the authors explored the correlates for nocturia and their population-level impact. In 2003–2004, questionnaires were mailed to 6,000 subjects (aged 18–79 years) randomly identified from the Finnish Population Register (62.4% participated; 53.7% were female). Questionnaires contained items on medical conditions, medications, lifestyle, sociodemographic and reproductive factors, urinary symptoms, and snoring. Nocturia was defined as ≥2 voids/night. In age-adjusted analyses, factors associated with nocturia were entered into a multivariate model. Backward elimination was used to select variables for the final model, with adjustment for confounding. Although numerous correlates were identified, none affected ≥50% of nocturia cases of both sexes. The factors with the greatest impact at the population level were (urinary) urgency (attributable number/1,000 subjects (AN) = 24), benign prostatic hyperplasia (AN = 19), and snoring (AN = 16) for men and overweight and obesity (AN = 40), urgency (AN = 24), and snoring (AN = 17) for women. Moreover, correlates included prostate cancer and antidepressant use for men, coronary artery disease and diabetes for women, and restless legs syndrome and obesity for both sexes. Although several correlates were identified, none accounted for a substantial proportion of the population burden, highlighting the multifactorial etiology of nocturia

    Regulation of the DNA Damage Response and Gene Expression by the Dot1L Histone Methyltransferase and the 53Bp1 Tumour Suppressor

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    Dot1L, a histone methyltransferase that targets histone H3 lysine 79 (H3K79), has been implicated in gene regulation and the DNA damage response although its functions in these processes remain poorly defined.Using the chicken DT40 model system, we generated cells in which the Dot1L gene is disrupted to examine the function and focal recruitment of the 53Bp1 DNA damage response protein. Detailed kinetic and dose response assays demonstrate that, despite the absence of H3K79 methylation demonstrated by mass spectrometry, 53Bp1 focal recruitment is not compromised in these cells. We also describe, for the first time, the phenotypes of a cell line lacking both Dot1L and 53Bp1. Dot1L⁻/⁻ and wild type cells are equally resistant to ionising radiation, whereas 53Bp1⁻/⁻/Dot1L⁻/⁻ cells display a striking DNA damage resistance phenotype. Dot1L and 53Bp1 also affect the expression of many genes. Loss of Dot1L activity dramatically alters the mRNA levels of over 1200 genes involved in diverse biological functions. These results, combined with the previously reported list of differentially expressed genes in mouse ES cells knocked down for Dot1L, demonstrates surprising cell type and species conservation of Dot1L-dependent gene expression. In 53Bp1⁻/⁻ cells, over 300 genes, many with functions in immune responses and apoptosis, were differentially expressed. To date, this is the first global analysis of gene expression in a 53Bp1-deficient cell line.Taken together, our results uncover a negative role for Dot1L and H3K79 methylation in the DNA damage response in the absence of 53Bp1. They also enlighten the roles of Dot1L and 53Bp1 in gene expression and the control of DNA double-strand repair pathways in the context of chromatin

    Differentiation and displacement: Unpicking the relationship between accounts of illness and social structure

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    This article seeks to unpack the relationship between social structure and accounts of illness. Taking dentine hypersensitivity as an example, this article explores the perspective that accounts of illness are sense-making processes that draw on a readily available pool of meaning. This pool of meaning is composed of a series of distinctions that make available a range of different lines of communication and action about such conditions. Such lines of communication are condensed and preserved over time and are often formed around a concept and its counter concept. The study of such processes is referred to as semantic analysis and involves drawing on the tools and techniques of conceptual history. This article goes on to explore how the semantics of dentine hypersensitivity developed. It illustrates how processes of social differentiation led to the concept being separated from the more dominant concept of dentine sensitivity and how it was medicalised, scientised and economised. In short, this study seeks to present the story of how society has developed a specific language for communicating about sensitivity and hypersensitivity in teeth. In doing so, it proposes that accounts of dentine hypersensitivity draw on lines of communication that society has preserved over time
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