Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

Clasp knife in the gut: a case report

BACKGROUND: A wide range of foreign bodies has been retrieved from the gut and reported. The presentation may be in the form of complications like intestinal obstruction, perforation and formation of abscesses etc but there is no case report of a half open clasp knife being retrieved from the ileum, the patient having thrived, in spite of its presence for a period of eight months. CASE PRESENTATION: A 30-year-old administrative clerk had undergone emergency abdominal surgery eight months previously under mysterious circumstances at a remote district hospital and had recovered completely. Later the blade of a knife was accidentally detected when an X ray of the abdomen was done during a routine follow-up visit to his family physician. Surgery revealed a clasp knife in the ileum, which was retrieved. The presence of an entero-enteric fistula short circuiting the loop was the secret of his earlier survival. CONCLUSIONS: To the best of our information this is the first case-report of a clasp knife in the gut and of the patient thriving in spite of its presence. We report here the dramatic sequence of events

Capsular synovial metaplasia mimicking silicone leak of a breast prosthesis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Synovial metaplasia around a prosthesis and in particular around silicone breast implants has been noted by various investigators, but has unknown clinical significance. We report on a patient where a large amount of synovial fluid mimicked rupture of an implant. We believe this to be an unusual clinical presentation of this phenomenon. Review of the English language literature failed to identify a comparable case.</p> <p>Case presentation</p> <p>A 25-year-old woman had undergone bilateral breast augmentation for cosmetic reasons. One implant was subsequently subjected to two attempts at expansion to correct asymmetry. The patient was later found to have a large quantity of viscous fluid around the port of that same prosthesis. Histological assessment of the implant had consequently confirmed capsular synovial metaplasia. This had initially caused the suspicion of a silicone 'bleed' from the implant and had resulted in an unnecessary explantation.</p> <p>Conclusion</p> <p>Capsular synovial metaplasia should be ruled out before the removal of breast implants where a leak is suspected. Manipulation and expansion of an implant may be risk factors for the development of synovial metaplasia.</p

Magnetic Catalysis and Quantum Hall Ferromagnetism in Weakly Coupled Graphene

We study the realization in a model of graphene of the phenomenon whereby the tendency of gauge-field mediated interactions to break chiral symmetry spontaneously is greatly enhanced in an external magnetic field. We prove that, in the weak coupling limit, and where the electron-electron interaction satisfies certain mild conditions, the ground state of charge neutral graphene in an external magnetic field is a quantum Hall ferromagnet which spontaneously breaks the emergent U(4) symmetry to U(2)XU(2). We argue that, due to a residual CP symmetry, the quantum Hall ferromagnet order parameter is given exactly by the leading order in perturbation theory. On the other hand, the chiral condensate which is the order parameter for chiral symmetry breaking generically obtains contributions at all orders. We compute the leading correction to the chiral condensate. We argue that the ensuing fermion spectrum resembles that of massive fermions with a vanishing U(4)-valued chemical potential. We discuss the realization of parity and charge conjugation symmetries and argue that, in the context of our model, the charge neutral quantum Hall state in graphene is a bulk insulator, with vanishing longitudinal conductivity due to a charge gap and Hall conductivity vanishing due to a residual discrete particle-hole symmetry.Comment: 35 page

Phenomenological Consequences of sub-leading Terms in See-Saw Formulas

Several aspects of next-to-leading (NLO) order corrections to see-saw formulas are discussed and phenomenologically relevant situations are identified. We generalize the formalism to calculate the NLO terms developed for the type I see-saw to variants like the inverse, double or linear see-saw, i.e., to cases in which more than two mass scales are present. In the standard type I case with very heavy fermion singlets the sub-leading terms are negligible. However, effects in the percent regime are possible when sub-matrices of the complete neutral fermion mass matrix obey a moderate hierarchy, e.g. weak scale and TeV scale. Examples are cancellations of large terms leading to small neutrino masses, or inverse see-saw scenarios. We furthermore identify situations in which no NLO corrections to certain observables arise, namely for mu-tau symmetry and cases with a vanishing neutrino mass. Finally, we emphasize that the unavoidable unitarity violation in see-saw scenarios with extra fermions can be calculated with the formalism in a straightforward manner.Comment: 22 pages, matches published versio

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis user

Three little pieces for computer and relativity

Numerical relativity has made big strides over the last decade. A number of problems that have plagued the field for years have now been mostly solved. This progress has transformed numerical relativity into a powerful tool to explore fundamental problems in physics and astrophysics, and I present here three representative examples. These "three little pieces" reflect a personal choice and describe work that I am particularly familiar with. However, many more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation: 100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech Republic. To appear in the Proceedings (Edition Open Access). Collects results appeared in journal articles [72,73, 122-124