Hypercalcemia in a patient with disseminated paracoccidioidomycosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of <it>Paracoccidioides brasiliensis </it>and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia.</p> <p>Case presentation</p> <p>We report the case of a 22-year-old man in whom disseminated infection with paracoccidioidomycosis was associated with hypercalcemia. The patient had a high normal serum level of 1,25-dihydroxyvitamin D and a suppressed parathyroid hormone value, an indication that the hypercalcemia was not mediated by parathyroid hormone and might be associated with 1,25-dihydroxyvitamin D.</p> <p>Conclusion</p> <p>The episode resolved readily with administration of corticosteroids, an outcome suggesting that this is an effective treatment of hypercalcemia of this origin. On follow-up, while receiving antifungal therapy for <it>P. brasiliensis </it>the patient's calcium values remained normal.</p

Significance of Elevated Blood Metal Ion Levels in Patients with Metal-on-Metal Prostheses: An Evaluation of Oxidative Stress Markers

It is widely known that cobalt and chromium ions can enhance the production of reactive oxygen species, known to be damaging to cells by disturbing their redox status and then generating oxidative stress. The aim of the present study was to determine if increased metal ion levels induce a state of oxidative stress in patients with metal-on-metal (MM) hip arthroplasty. Results indicated that there was no significant difference in the concentration of oxidative stress markers (total antioxidants, peroxides, and nitrated proteins) in the patients with MM bearings compared to patients without prostheses. The activity antioxidant enzymes was stable (catalase and glutathione peroxidase) or slightly decreased (superoxide dismutase and heme oxygenase-1) over time. This work is the first to determine the biological effects of metal ions released from MM hip implants with regards to mid-term systemic oxidative stress and showed that the increased levels of Co and Cr ions are not associated with significant oxidative stress damage in the plasma of patients with these implants

Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells

HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol

Epistatic Association Mapping in Homozygous Crop Cultivars

The genetic dissection of complex traits plays a crucial role in crop breeding. However, genetic analysis and crop breeding have heretofore been performed separately. In this study, we designed a new approach that integrates epistatic association analysis in crop cultivars with breeding by design. First, we proposed an epistatic association mapping (EAM) approach in homozygous crop cultivars. The phenotypic values of complex traits, along with molecular marker information, were used to perform EAM. In our EAM, all the main-effect quantitative trait loci (QTLs), environmental effects, QTL-by-environment interactions and QTL-by-QTL interactions were included in a full model and estimated by empirical Bayes approach. A series of Monte Carlo simulations was performed to confirm the reliability of the new method. Next, the information from all detected QTLs was used to mine novel alleles for each locus and to design elite cross combination. Finally, the new approach was adopted to dissect the genetic basis of seed length in 215 soybean cultivars obtained, by stratified random sampling, from 6 geographic ecotypes in China. As a result, 19 main-effect QTLs and 3 epistatic QTLs were identified, more than 10 novel alleles were mined and 3 elite parental combinations, such as Daqingdou and Zhengzhou790034, were predicted

Dengue-2 Structural Proteins Associate with Human Proteins to Produce a Coagulation and Innate Immune Response Biased Interactome

<p>Abstract</p> <p>Background</p> <p>Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem.</p> <p>Methods</p> <p>A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology.</p> <p>Results</p> <p>Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis.</p> <p>Conclusions</p> <p>Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti-viral response processes, and predicts that the interaction of dengue proteins with a proposed human protein interaction network produces a modified biological outcome that may be behind the hallmark pathologies of dengue infection.</p

Encouraging female entrepreneurship in Jordan: environmental factors, obstacles and challenges

The number of female entrepreneurs and their contribution to the economy is steadily rising. Yet research suggests that female entrepreneurs face more challenges and barriers than their male counterparts. This is expected to be even more prevalent in Islamic contexts, which are characterised by conservative and patriarchal societies. In this research, 254 female business students from a private and a public university responded to a questionnaire that gauges their perceptions about potential barriers to entrepreneurship in Jordan and whether the business education they are receiving helps to prepare them for future entrepreneurial activity. Our results help to form a basis on which a deeper understanding of the phenomena can be achieved through more in depth future research. Among the main environmental factors that worry potential female entrepreneurs are the weakness of Jordanian economy, lack of finance, fear of risk, gender inequality and inability to maintain a work and private life balance. Our results also show that students are really not aware of the opportunities available to them and are unable to make a proper assessment. We call on both universities and the Jordanian government to put more emphasis on practical entrepreneurial education and encouraging women to play a much more active role within the workforce