Ectopic ureter associated with uterine didelphys and obstructed hemivagina: preoperative diagnosis by MRI

Uterine didelphys with obstructed hemivagina and ipsilateral renal anomalies is a rare congenital malformation of the female urogenital tract. While the urinary anomalies almost always involve renal agenesis, we report a rare case of a 17-year-old girl with the malformation associated with ectopic ureteral insertion into the obstructed hemivagina, which was diagnosed preoperatively by MR imaging. To the best of our knowledge, preoperative MR imaging diagnosis of the ectopic ureter associated with this syndrome has not been previously reported. Accurate preoperative diagnosis of ectopic ureteral insertion associated with this syndrome is important for surgical planning

A Dual-Color Fluorescence-Based Platform to Identify Selective Inhibitors of Akt Signaling

Background: Inhibition of Akt signaling is considered one of the most promising therapeutic strategies for many cancers. However, rational target-orientated approaches to cell based drug screens for anti-cancer agents have historically been compromised by the notorious absence of suitable control cells. Methodology/Principal Findings: In order to address this fundamental problem, we have developed BaFiso, a live-cell screening platform to identify specific inhibitors of this pathway. BaFiso relies on the co-culture of isogenic cell lines that have been engineered to sustain interleukin-3 independent survival of the parental Ba/F3 cells, and that are individually tagged with different fluorescent proteins. Whilst in the first of these two lines cell survival in the absence of IL-3 is dependent on the expression of activated Akt, the cells expressing constitutively-activated Stat5 signaling display IL-3 independent growth and survival in an Akt-independent manner. Small molecules can then be screened in these lines to identify inhibitors that rescue IL-3 dependence. Conclusions/Significance: BaFiso measures differential cell survival using multiparametric live cell imaging and permits selective inhibitors of Akt signaling to be identified. BaFiso is a platform technology suitable for the identification of smal

Geographical distribution of publications in the field of medical education

BACKGROUND: The geographical distribution of publications as an indicator of the research productivity of individual countries, regions or institutions has become a field of interest. We investigated the geographical distribution of contributions to the two leading journals in the field of medical education, Academic Medicine and Medical Education. METHODS: PubMed was used to search Medline. For both journals all journal articles in each year from 1995 to 2000 were included into the study. Then the affiliation was retrieved from the affiliation field of the MEDLINE format. If this was not possible, it was obtained from the paper version of the journal. RESULTS: Academic Medicine published contributions from 25 countries between 1995 and 2000. Authors from 50 countries contributed to Medical Education in the same period of time. Authors from the USA and Canada wrote ca. 95% off all articles in Academic Medicine, whereas authors from the UK, Australia, the USA, Canada and the Netherlands were responsible for ca. 74% of all articles in Medical Education in the investigated period of time. CONCLUSIONS: While many countries contributed to both journals, only a few of them were responsible for the majority of all articles

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Identification of alternative splice variants in Aspergillus flavus through comparison of multiple tandem MS search algorithms

<p>Abstract</p> <p>Background</p> <p>Database searching is the most frequently used approach for automated peptide assignment and protein inference of tandem mass spectra. The results, however, depend on the sequences in target databases and on search algorithms. Recently by using an alternative splicing database, we identified more proteins than with the annotated proteins in <it>Aspergillus flavus</it>. In this study, we aimed at finding a greater number of eligible splice variants based on newly available transcript sequences and the latest genome annotation. The improved database was then used to compare four search algorithms: Mascot, OMSSA, X! Tandem, and InsPecT.</p> <p>Results</p> <p>The updated alternative splicing database predicted 15833 putative protein variants, 61% more than the previous results. There was transcript evidence for 50% of the updated genes compared to the previous 35% coverage. Database searches were conducted using the same set of spectral data, search parameters, and protein database but with different algorithms. The false discovery rates of the peptide-spectrum matches were estimated < 2%. The numbers of the total identified proteins varied from 765 to 867 between algorithms. Whereas 42% (1651/3891) of peptide assignments were unanimous, the comparison showed that 51% (568/1114) of the RefSeq proteins and 15% (11/72) of the putative splice variants were inferred by all algorithms. 12 plausible isoforms were discovered by focusing on the consensus peptides which were detected by at least three different algorithms. The analysis found different conserved domains in two putative isoforms of UDP-galactose 4-epimerase.</p> <p>Conclusions</p> <p>We were able to detect dozens of new peptides using the improved alternative splicing database with the recently updated annotation of the <it>A. flavus </it>genome. Unlike the identifications of the peptides and the RefSeq proteins, large variations existed between the putative splice variants identified by different algorithms. 12 candidates of putative isoforms were reported based on the consensus peptide-spectrum matches. This suggests that applications of multiple search engines effectively reduced the possible false positive results and validated the protein identifications from tandem mass spectra using an alternative splicing database.</p

Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.OBJECT: Complement activation has been suggested to play a role in the development of secondary injuries following traumatic brain injury (TBI). The present study was initiated in order to analyze complement activation in relation to the primary brain injury and to secondary insults, frequently occurring following TBI. METHODS: Twenty patients suffering from severe TBI (Glasgow coma score ≤ 8) were included in the study. The "membrane attack complex," C5b9, which is the cytolytic end product of the complement system was analyzed in cerebrospinal fluid (CSF). The degree of brain tissue damage was assessed using the release of S100B and neuron-specific enolase (NSE) to the CSF and blood. The blood-brain barrier was assessed using the CSF/serum quotient of albumin (Q (A)). RESULTS: Following impact, initial peaks (0-48 h) of C5b9, S100B, and NSE with a concomitant loss of integrity of the blood-brain barrier were observed. Secondary insults at the intensive care unit were monitored. Severe secondary insults were paralleled by a more pronounced complement activation (C5b9 in CSF) as well as increased levels of S100B (measured in CSF), but not with NSE. CONCLUSION: This human study indicates that complement activation in the brain is triggered not only by the impact of trauma per se but also by the amount of secondary insults that frequently occur at the scene of accident as well as during treatment in the neurointensive care unit. Complement activation and in particular the end product C5b9 may in turn contribute to additional secondary brain injuries by its membrane destructive properties

A supramolecular helix that disregards chirality

The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self-assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks

Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer Institution

Background: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.info:eu-repo/semantics/publishedVersio

An average/deprivation/inequality (ADI) analysis of chronic disease outcomes and risk factors in Argentina

<p>Abstract</p> <p>Background</p> <p>Recognition of the global economic and epidemiological burden of chronic non-communicable diseases has increased in recent years. However, much of the research on this issue remains focused on individual-level risk factors and neglects the underlying social patterning of risk factors and disease outcomes.</p> <p>Methods</p> <p>Secondary analysis of Argentina's 2005 <it>Encuesta Nacional de Factores de Riesgo </it>(National Risk Factor Survey, <it>N </it>= 41,392) using a novel analytical strategy first proposed by the United Nations Development Programme (UNDP), which we here refer to as the Average/Deprivation/Inequality (ADI) framework. The analysis focuses on two risk factors (unhealthy diet and obesity) and one related disease outcome (diabetes), a notable health concern in Latin America. Logistic regression is used to examine the interplay between socioeconomic and demographic factors. The ADI analysis then uses the results from the logistic regression to identify the most deprived, the best-off, and the difference between the two ideal types.</p> <p>Results</p> <p>Overall, 19.9% of the sample reported being in poor/fair health, 35.3% reported not eating any fruits or vegetables in five days of the week preceding the interview, 14.7% had a BMI of 30 or greater, and 8.5% indicated that a health professional had told them that they have diabetes or high blood pressure. However, significant variation is hidden by these summary measures. Educational attainment displayed the strongest explanatory power throughout the models, followed by household income, with both factors highlighting the social patterning of risk factors and disease outcomes. As educational attainment and household income increase, the probability of poor health, unhealthy diet, obesity, and diabetes decrease. The analyses also point toward important provincial effects and reinforce the notion that both compositional factors (i.e., characteristics of individuals) and contextual factors (i.e., characteristics of places) are important in understanding the social patterning of chronic diseases.</p> <p>Conclusion</p> <p>The application of the ADI framework enables identification of the regions or groups worst-off for each outcome measure under study. This can be used to highlight the variation embedded within national averages; as such, it encourages a social perspective on population health indicators that is particularly attuned to issues of inequity. The ADI framework is an important tool in the evaluation of policies aiming to prevent or control chronic non-communicable diseases.</p

A proteomic approach to investigating gene cluster expression and secondary metabolite functionality in Aspergillus fumigatus.

A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Indirect identification of secondary metabolite cluster expression was also achieved, with proteins (n = 18) from LaeA-regulated clusters detected, including GliT encoded within the gliotoxin biosynthetic cluster. Biochemical analysis then revealed that gliotoxin significantly attenuates H2O2-induced oxidative stress in A. fumigatus (p>0.0001), confirming observations from proteomics data. A complementary 2-D/LC-MS/MS approach further elucidated significantly increased abundance (p<0.05) of proliferating cell nuclear antigen (PCNA), NADH-quinone oxidoreductase and the gliotoxin oxidoreductase GliT, along with significantly attenuated abundance (p<0.05) of a heat shock protein, an oxidative stress protein and an autolysis-associated chitinase, when gliotoxin and H2O2 were present, compared to H2O2 alone. Moreover, gliotoxin exposure significantly reduced the abundance of selected proteins (p<0.05) involved in de novo purine biosynthesis. Significantly elevated abundance (p<0.05) of a key enzyme, xanthine-guanine phosphoribosyl transferase Xpt1, utilised in purine salvage, was observed in the presence of H2O2 and gliotoxin. This work provides new insights into the A. fumigatus proteome and experimental strategies, plus mechanistic data pertaining to gliotoxin functionality in the organism