1,659 research outputs found
Pyoderma gangrenosum: a presenting sign of myelodysplastic syndrome in undiagnosed Fanconi anemia
A 26-year-old man with a history of congenital bilateral microtia, unilateral renal agenesis, left aural atresia, and right external auditory canal occlusion admitted for right rib cartilage graft harvest and left ear re-construction. Following surgery, an ulceration with violaceous borders and a yellow fibrinous base unresponsive to broad-spectrum antibiotics developed at the harvest site. The wound was expanding and not responsive to systemic broad-spectrum antibiotics. Biopsy revealed a dense dermal infiltrate of neutrophils with negative tissue cultures consistent with pyoderma gangrenosum (PG). He was treated with systemic, intralesional, and topical steroids, as well as doxycycline. Three weeks after the diagnosis of PG, he was found to have persistent anemia and leukopenia. Bone marrow aspiration analysis was consistent with hypocellular myelodysplastic syndrome and genetic testing was consistent with Fanconi anemia. There is a well-known association of PG with hematological disorders. Fanconi anemia is a rare genetic hematologic disorder with congenital defects leading to bone marrow failure and malignancy in long-standing disease. In our patient, we consider his development of PG a paraneoplastic sign associated with the onset of his hypocellular myelodysplastic syndrome
Recent advances in management of renal cancer
Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years, resulting in prolonged progression-free and overall survival
Advanced textile applications for primary aircraft structures
Advanced composite primary structural concepts have been evaluated for low cost, damage tolerant structures. Development of advanced textile preforms for fuselage structural applications with resin transfer molding and powder epoxy material is now under development
Applied Tests of Design Skills — Part 1: Divergent Thinking
A number of cognitive skills relevant to conceptual design were identified previously. They include divergent thinking (DT), visual thinking (VT), spatial reasoning (SR), qualitative reasoning (QR), and problem formulation (PF). A battery of standardized tests is being developed for these design skills. This paper focuses only on the divergent thinking test. This particular test has been given to over 500 engineering students and a smaller number of practicing engineers. It is designed to evaluate four direct measures (fluency, flexibility, originality, and quality) and four indirect measures (abstractability, afixability, detailability, and decomplexability). The eight questions on the test overlap in some measures and the responses can be used to evaluate several measures independently (e.g., fluency and originality can be evaluated separately from the same idea set). The data on the twenty-three measured variables were factor analyzed using both exploratory and confirmatory procedures. A four-factor solution with correlated (oblique) factors was deemed the best available solution after examining solutions with more factors. The indirect measures did not appear to correlate strongly either among themselves or with the other direct measures. The four-factor structure was then taken into a confirmatory factor analytic procedure that adjusted for the missing data. It was found to provide a reasonable fit. Estimated correlations among the four factors (F) ranged from a high of 0.32 for F1 and F2 to a low of 0.06 for F3 and F4. All factor loadings were statistically significant
Pregnancy outcome in patients with fibroid: a retrospective study
Background: Fibroids are benign smooth muscle cell tumour of the uterus. In some patients of pregnancy associated with fibroid, it does not affect the outcome of pregnancy. On the other hand, various complications have been reported. The aim of our study was to evaluate the outcome in antenatal women with fibroids.Methods: This retrospective study was conducted at tertiary care center, obstetrics & gynecology department over a period of eighteen months between June 2018 to November 2019. Total 26 pregnant patients with >3 cm fibroid was included in the study. They were followed during antenatal period. Maternal age, parity, size of fibroid, complications during pregnancy, labour, and delivery, mode of delivery and indications of cesarean section were noted.Results: Out of 26 patients, 15 (57.6%) were between 26-30 years of age group and 16 (61.53%) were multigravidas. Normal vaginal delivery occurred in 8 (33.33%), while 16 (66.66%) delivered by caesarean section. There were 9 (34.61%) patients who had no complication whereas 17 (65.38%) had some complication. Pain was present in 8 (30.76%). PROM and preterm labour were present in 3 (18.75%) and 5 (19.23%) respectively. PPH was present in 2 (7.69%).Conclusions: Pregnant patients who have fibroids are to be carefully screened in the antenatal period, so as to have a regular follow up. The widespread use of ultrasonography has facilitated diagnosis and management of fibroids in pregnancy. The site and size of fibroid is very important to predict its effect on pregnancy
Real-Time MRI-Guided Catheter Tracking Using Hyperpolarized Silicon Particles
Visualizing the movement of angiocatheters during endovascular interventions is typically accomplished using x-ray fluoroscopy. There are many potential advantages to developing magnetic resonance imaging-based approaches that will allow three-dimensional imaging of the tissue/vasculature interface while monitoring other physiologically-relevant criteria, without exposing the patient or clinician team to ionizing radiation. Here we introduce a proof-of-concept development of a magnetic resonance imaging-guided catheter tracking method that utilizes hyperpolarized silicon particles. The increased signal of the silicon particles is generated via low-temperature, solid-state dynamic nuclear polarization, and the particles retain their enhanced signal for ?40?minutes—allowing imaging experiments over extended time durations. The particles are affixed to the tip of standard medical-grade catheters and are used to track passage under set distal and temporal points in phantoms and live mouse models. With continued development, this method has the potential to supplement x-ray fluoroscopy and other MRI-guided catheter tracking methods as a zero-background, positive contrast agent that does not require ionizing radiation
The driver landscape of sporadic chordoma.
Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma
Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells
<p>Abstract</p> <p>Background</p> <p>Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.</p> <p>Results</p> <p>SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.</p> <p>Conclusions</p> <p>SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.</p
Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP
Background: Nonphotosensitive trichothiodystrophy (TTDN) is a rare autosomal recessive disorder of neuroectodermal origin. The condition is marked by hair abnormalities, intellectual impairment, nail dystrophies and susceptibility to infections but with no UV sensitivity.
Methods: We identified three consanguineous Pakistani families with varied TTDN features and used homozygosity mapping, linkage analysis, and Sanger and exome sequencing in order to identify pathogenic variants. Haplotype analysis was performed and haplotype age estimated. A splicing assay was used to validate the effect of the MPLKIP splice variant on expression.
Results: Affected individuals from all families exhibit several TTDN features along with a heart-specific feature, i.e. mitral regurgitation. Exome sequencing in the probands from families ED168 and ED241 identified a homozygous splice mutation c.339 + 1G > A within MPLKIP. The same splice variant co-segregates with TTDN in a third family ED210. The MPLKIP splice variant was not found in public databases, e.g. the Exome Aggregation Consortium, and in unrelated Pakistani controls. Functional analysis of the splice variant confirmed intron retention, which leads to protein truncation and loss of a phosphorylation site. Haplotype analysis identified a 585.1-kb haplotype which includes the MPLKIP variant, supporting the existence of a founder haplotype that is estimated to be 25,900 years old.
Conclusion: This study extends the allelic and phenotypic spectra of MPLKIP-related TTDN, to include a splice variant that causes cardiomyopathy as part of the TTDN phenotype
Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial
IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved
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