1,248 research outputs found

    Incidental Detection of Interstitial Pregnancy on CT Imaging

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    Ectopic pregnancy is a potentially life-threatening condition. Detection of ectopic pregnancy on CT images is rare. In this case, we describe the CT findings of interstitial pregnancy both before and after rupture. If CT images demonstrate the presence of a strong enhancing ring-like mass in the pelvis, ectopic pregnancy should be considered

    The Spectrum of Benign Esophageal Lesions: Imaging Findings

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    Benign esophageal lesions occur in various diseases. Barium studies are useful for the evaluation of mucosal surface lesions but provide little information about the extramucosal extent of disease. Computed tomography and magnetic resonance imaging, on the other hand, permit the assessment of wall thickness, mediastinal involvement, adjacent lymphadenopathy, and distant spread. In diseases such as fibrovascular polyps, duplication cysts, scleroderma, trauma, caustic esophagitis, hiatal hernia, esophageal diverticulum, achalasia, and paraesophageal varices, the findings of imaging studies are specific, obviating the need for further invasive diagnostic work-up. The advent of helical computed tomography and its volume data set allows the acquisition of multiplanar images, and magnetic resonance imaging is useful both for this and for tissue characterization. Thus, multiplanar cross-sectional imaging further extends the role of imaging modalities to the evaluation of benign esophageal lesions. Through an awareness of the multiplanar cross-sectional appearances of various benign esophageal lesions, the radiologist can play an important role in the detection, diagnosis, further diagnostic planning, and treatment of the diseases in which they occur

    Role of autophagy in diabetes and endoplasmic reticulum stress of pancreatic β-cells

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    Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic β-cells producing insulin. Autophagy plays a crucial role in cellular homeostasis through degradation and recycling of organelles such as mitochondria or endoplasmic reticulum (ER). Here we discussed the role of β-cell autophagy in development of diabetes, based on our own studies using mice with β-cell-specific deletion of Atg7 (autophagy-related 7), an important autophagy gene, and studies by others. β-cell-specific Atg7-null mice showed reduction in β-cell mass and pancreatic insulin content. Insulin secretory function ex vivo was also impaired, which might be related to organelle dysfunction associated with autophagy deficiency. As a result, β-cell-specific Atg7-null mice showed hypoinsulinemia and hyperglycemia. However, diabetes never developed in those mice. Obesity and/or lipid are physiological ER stresses that can precipitate β-cell dysfunction. Our recent studies showed that β-cell-specific Atg7-null mice, when bred with ob/ob mice, indeed become diabetic. Thus, autophagy deficiency in β-cells could be a precipitating factor in the progression from obesity to diabetes due to inappropriate response to obesity-induced ER stress

    SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

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    BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

    Marginalization of end-use technologies in energy innovation for climate protection

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    Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

    Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

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    The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

    Tapping into the glial reservoir: cells committed to remaining uncommitted

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    The development and maturation of the oligodendrocyte requires a series of highly orchestrated events that coordinate the proliferation and differentiation of the oligodendrocyte precursor cell (OPC) as well as the spatiotemporal regulation of myelination. In recent years, widespread interest has been devoted to the therapeutic potential of adult OPCs scattered throughout the central nervous system (CNS). In this review, we highlight molecular mechanisms controlling OPC differentiation during development and the implication of these mechanisms on adult OPCs for remyelination. Cell-autonomous regulators of differentiation and the heterogeneous microenvironment of the developing and the adult CNS may provide coordinated inhibitory cues that ultimately maintain a reservoir of uncommitted glia

    The limited usefulness of real-time 3-dimensional echocardiography in obtaining normal reference ranges for right ventricular volumes

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    <p>Abstract</p> <p>Background</p> <p>To obtain normal reference ranges and intraobserver variability for right ventricular (RV) volume indexes (VI) and ejection fraction (EF) from apical recordings with real-time 3-dimensional echocardiography (RT3DE), and similarly for RV area indexes (AI) and area fraction (AF) with 2-dimensional echocardiography (2DE).</p> <p>Methods</p> <p>166 participants; 79 males and 87 females aged between 29–79 years and considered free from clinical and subclinical cardiovascular disease. Normal ranges are defined as 95% reference values and reproducibility as coefficients of variation (CV) for repeated measurements.</p> <p>Results</p> <p>None of the apical recordings with RT3DE and 2DE included the RV outflow tract. Upper reference values were 62 ml/m<sup>2 </sup>for RV end-diastolic (ED) VI and 24 ml/m<sup>2 </sup>for RV end-systolic (ES) VI. Lower normal reference value for RVEF was 41%. The respective reference ranges were 17 cm<sup>2</sup>/m<sup>2 </sup>for RVEDAI, 11 cm<sup>2</sup>/m<sup>2 </sup>for RVESAI and 27% for RVAF. Males had higher upper normal values for RVEDVI, RVESVI and RVEDAI, and a lower limit than females for RVEF and RVAF. Weak but significant negative correlations between age and RV dimensions were found with RT3DE, but not with 2DE. CVs for repeated measurements ranged between 10% and 14% with RT3DE and from 5% to 14% with 2DE.</p> <p>Conclusion</p> <p>Although the normal ranges for RVVIs and RVAIs presented in this study reflect RV inflow tract dimensions only, the data presented may still be regarded as a useful tool in clinical practice, especially for RVEF and RVAF.</p

    Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: A double-blind randomised placebo controlled 6-month trial

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    <p>Abstract</p> <p>Background</p> <p>Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50–70 years.</p> <p>Methods</p> <p>We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A<sub>1c</sub>(GHbA<sub>1c</sub>). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale.</p> <p>Results</p> <p>Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA<sub>1c </sub>(mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred.</p> <p>Conclusion</p> <p>This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN55819922</p

    Clinical Role of Interstitial Pneumonia in Patients with Scrub Typhus: A Possible Marker of Disease Severity

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    Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known. This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus. We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus. We then compared these clinical factors between patients with and without IP. We also studied the relationship between IP and other chest radiographic findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49). The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP. Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus
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