Renal papillary carcinoma developed in a kidney transplant recipient with late IgA-nephropathy

With improvements in immunosuppressive therapy, patient and graft survival in renal transplant recipients have been prolonged. Increasing donor age and patient survival rates have been related to an increase in the number of de novo tumors. Posttransplant malignancy in these patients is an important cause of graft loss and death in these patients. Among cancers occurring after a kidney transplant, renal cell carcinoma is the fifth most common malignancy after lymphoproliferative disorders, and skin, gastrointestinal, and lung cancers. When nonmelanoma skin cancers and in situ carcinoma of the cervix are excluded from malignancies, renal cell carcinoma accounts for 2% of all cancers in the general population, which increases to 5% in solid-organ recipients. The majority of renal cell carcinomas found in transplant recipients develop in the recipient 's native kidneys, but only 9% of tumors develop in the allograft itself. Tumors transmitted by donors represent only 0.02% to 0.2% of cases. Most de novo allograft renal cell carcinomas are single tumors. The mechanisms of development of renal cell carcinoma in renal grafts are not completely understood

Directing reaction pathways via in situ control of active site geometries in PdAu single-atom alloy catalysts

The atomic scale structure of the active sites in heterogeneous catalysts is central to their reactivity and selectivity. Therefore, understanding active site stability and evolution under different reaction conditions is key to the design of efficient and robust catalysts. Herein we describe theoretical calculations which predict that carbon monoxide can be used to stabilize different active site geometries in bimetallic alloys and then demonstrate experimentally that the same PdAu bimetallic catalyst can be transitioned between a single-atom alloy and a Pd cluster phase. Each state of the catalyst exhibits distinct selectivity for the dehydrogenation of ethanol reaction with the single-atom alloy phase exhibiting high selectivity to acetaldehyde and hydrogen versus a range of products from Pd clusters. First-principles based Monte Carlo calculations explain the origin of this active site ensemble size tuning effect, and this work serves as a demonstration of what should be a general phenomenon that enables in situ control over catalyst selectivity

Maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years

Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptom chronicity on children’s emotional and behavioral functioning at 24 months. Following postnatal screening mothers (n = 296) were identified as having MDD, GAD, MDD and GAD, or no disorder at 3 months postnatal; the average age was 32.3 (SD = 5.0), 91.9% self-identified as Caucasian, and 62.2% were married. Maternal disorder symptom severity was assessed by questionnaires and structured interview at 3, 6, 10, 14, and 24 months postpartum. At 24 months, child emotional negativity and behavior were assessed using questionnaires and by direct observation. Latent trait-state-occasion modeling was used to represent maternal disorder symptom chronicity; both stable trait and time-specific occasion portions of maternal symptomatology were examined in relation to child outcomes. Only the stable trait portion of maternal MDD and GAD symptom severity were related to maternal report of child behavior problems and higher levels of emotional negativity. Persistent maternal MDD, but not GAD, symptom severity was related to higher levels of child emotional negativity as measured observationally. These data suggest that children’s behavior problems and emotional negativity are adversely affected by persistent maternal depression, and possibly anxiety. This has implications for interventions to prevent negative effects of postnatal psychopathology on children

First-principles design of a single-atom–alloy propane dehydrogenation catalyst

The complexity of heterogeneous catalysts means that a priori design of new catalytic materials is difficult, but the well-defined nature of single-atom–alloy catalysts has made it feasible to perform unambiguous theoretical modeling and precise surface science experiments. Herein we report the theory-led discovery of a rhodium-copper (RhCu) single-atom–alloy catalyst for propane dehydrogenation to propene. Although Rh is not generally considered for alkane dehydrogenation, first-principles calculations revealed that Rh atoms disperse in Cu and exhibit low carbon-hydrogen bond activation barriers. Surface science experiments confirmed these predictions, and together these results informed the design of a highly active, selective, and coke-resistant RhCu nanoparticle catalyst that enables low-temperature nonoxidative propane dehydrogenation

Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions

BACKGROUND: Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999. RESULTS: Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues. CONCLUSIONS: Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected

The Mediterranean Island Wetlands (MedIsWet) inventory: strengths and shortfalls of the currently available floristic data

MedIsWet (Conservation of the island wetlands of the Mediterranean Basin) is a MAVA funded project which aims at investigating all seasonal or permanent island wetlands both natural and artificial, with a minimum extent of 0.1 hectares. More than 16,000 wetlands from almost all the Mediterranean, including islands from France, Italy, Malta, Croatia, Cyprus, Tunisia, Turkey, Greece and Spain were mapped. Over 2,500 of them were inventoried in the field and more than 500 scientific contributions catalogued. In total, more than 35,000 plant occurrences were uploaded, in a standardised and comparable way, on the national open-source web portals. These can be related to the recorded threats, uses and other spatially retrievable information. Here, we show strengths and shortfalls of the already available information about the floristic records. Although further improvements are needed, we discuss how these data can be used for research and policy actions and to develop conservation projects

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis

<p>Abstract</p> <p>Background</p> <p>Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools.</p> <p>Methods</p> <p>To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.</p> <p>Results</p> <p>Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA.</p> <p>Conclusion</p> <p>Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.</p

Global MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation, Invasion and Poor Clinical Outcome in Breast Cancer

Aberrant microRNA (miRNA) expression is associated with cancer and has potential diagnostic and prognostic value in various malignancies. In this study, we investigated miRNA profiling as a complementary tool to improve our understanding of breast cancer (BC) biology and to assess whether miRNA expression could predict clinical outcome of BC patients.In VitroJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system