1,826 research outputs found
Bilateral Popliteal Entrapment Syndrome in a Young Athlete Diagnosed with Ultrasound
Popliteal artery entrapment syndrome (PAES) occurs when the popliteal artery is compressed by abnormally developed or hypertrophied muscles adjacent to the popliteal fossa. When symptomatic, it most frequently presents with leg cramping while walking or running. We describe the case of an 18-year-old female runner presenting with claudication and exercise intolerance. After MRI was non-diagnostic, diagnostic ultrasound demonstrated that she had functional (Type VI) PAES. She subsequently underwent popliteal artery release surgery. Type VI PAES should be considered in young, healthy patients who present with claudication, particularly athletes
TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption
Plekhm1 is a large, multi-modular, adapter protein implicated in osteoclast vesicle trafficking and bone resorption. In patients, inactivating mutations cause osteopetrosis, and gain-of-function mutations cause osteopenia. Investigations of potential Plekhm1 interaction partners by mass spectrometry identified TRAFD1 (FLN29), a protein previously shown to suppress toll-like receptor signaling in monocytes/macrophages, thereby dampening inflammatory responses to innate immunity. We mapped the binding domains to the TRAFD1 zinc finger (aa 37-60), and to the region of Plekhm1 between its second pleckstrin homology domain and its C1 domain (aa 784-986). RANKL slightly increased TRAFD1 levels, particularly in primary osteoclasts, and the co-localization of TRAFD1 with Plekhm1 also increased with RANKL treatment. Stable knockdown of TRAFD1 in RAW 264.7 cells inhibited resorption activity proportionally to the degree of knockdown, and inhibited acidification. The lack of acidification occurred despite the presence of osteoclast acidification factors including carbonic anhydrase II, a3-V-ATPase, and the ClC7 chloride channel. Secretion of TRAP and cathepsin K were also markedly inhibited in knockdown cells. Truncated Plekhm1 in ia/ia osteopetrotic rat cells prevented vesicle localization of Plekhm1 and TRAFD1. We conclude that TRAFD1, in association with Plekhm1/Rab7-positive late endosomes-early lysosomes, has a previously unknown role in vesicle trafficking, acidification, and resorption in osteoclasts
Late widespread skeletal metastases from myxoid liposarcoma detected by MRI only
Background
Myxoid liposarcoma is the second most commonly occurring sub-type of liposarcomas. In contrast to other soft tissue sarcomas, it is known to have a tendency to spread toward extrapulmonary sites, such as soft tissues, retroperitoneum, and the peritoneal surface. Bony spread, however, is not as common.
Case presentation
We report an unusual case of diffuse skeletal metastases from myxoid liposarcoma occurring 13 years after treatment of the primary tumour in the left lower limb. The skeletal spread of the disease was demonstrated on MRI only after other imaging modalities (plain radiography, CT and TC99 bone scans) had failed to detect these metastases.
Conclusion
MRI is an extremely sensitive and specific screening tool in the detection of skeletal involvement in these types of sarcomas, and therefore, should be a part of the staging proces
The impact of induction chemotherapy on the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer
Background: Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. Patients and methods: In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. Results: Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. Conclusions: Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therap
The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.
Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes
Multichannel quantum-defect theory for ultracold atom-ion collisions
We develop an analytical model for ultracold atom-ion collisions using the
multichannel quantum-defect formalism. The model is based on the analytical
solutions of the r^-4 long-range potential and on the application of a frame
transformation between asymptotic and molecular bases. This approach allows the
description of the atom-ion interaction in the ultracold domain in terms of
three parameters only: the singlet and triplet scattering lengths, assumed to
be independent of the relative motion angular momentum, and the lead dispersion
coefficient of the asymptotic potential. We also introduce corrections to the
scattering lengths that improve the accuracy of our quantum-defect model for
higher order partial waves, a particularly important result for an accurate
description of shape and Feshbach resonances at finite temperature. The theory
is applied to the system composed of a 40Ca+ ion and a Na atom, and compared to
numerical coupled-channel calculations carried out using ab initio potentials.
For this particular system, we investigate the spectrum of bound states, the
rate of charge-transfer processes, and the collision rates in the presence of
magnetic Feshbach resonances at zero and finite temperature.Comment: 39 pages, 21 figure
Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics
How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities
Field-induced effects in the spin liquid candidate PbCuTeO
PbCuTeO is considered as one of the rare candidate materials for a
three-dimensional quantum spin liquid (QSL). This assessment was based on the
results of various magnetic experiments, performed mainly on polycrystalline
material. More recent measurements on single crystals revealed an even more
exotic behavior, yielding ferroelectric order below , accompanied by distinct lattice distortions, and a somewhat
modified magnetic response which is still consistent with a QSL. Here we report
on low-temperature measurements of various thermodynamic, magnetic and
dielectric properties of single crystalline PbCuTeO in magnetic fields
. The combination of these various probes allows us to
construct a detailed - phase diagram including a ferroelectric phase for
and a -induced magnetic phase at
. These phases are preceded by or coincide with a structural
transition from a cubic high-temperature phase into a distorted non-cubic
low-temperature state. The phase diagram discloses two quantum critical points
(QCPs) in the accessible field range, a ferroelectric QCP at =
and a magnetic QCP at = . Field-induced
lattice distortions, observed in the state at and which are
assigned to the effect of spin-orbit interaction of the Cu-ions, are
considered as the key mechanism by which the magnetic field couples to the
dielectric degrees of freedom in this material
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