Radiation-induced morphea of the breast: a case report

Radiation-induced morphea (RIM) of the breast is a rare complication of radiotherapy. It is disfiguring, painful and defeats the purpose of achieving a good cosmesis in breast-conservation surgery. This report describes a severe case of RIM in a breast cancer patient together with photographic illustrations of the serial changes over time and histopathology slides. A review of the literature is provided

Sorafenib decreases proliferation and induces apoptosis of prostate cancer cells by inhibition of the androgen receptor and Akt signaling pathways

Antihormonal and chemotherapy are standard treatments for nonorgan-confined prostate cancer. The effectivity of these therapies is limited and the development of alternative approaches is necessary. In the present study, we report on the use of the multikinase inhibitor sorafenib in a panel of prostate cancer cell lines and their derivatives which mimic endocrine and chemotherapy resistance. 3H-thymidine incorporation assays revealed that sorafenib causes a dose-dependent inhibition of proliferation of all cell lines associated with downregulation of cyclin-dependent kinase 2 and cyclin D1 expression. Apoptosis was induced at 2 μM of sorafenib in androgen-sensitive cells, whereas a higher dose of the drug was needed in castration-resistant cell lines. Sorafenib stimulated apoptosis in prostate cancer cell lines through downregulation of myeloid cell leukemia-1 (MCL-1) expression and Akt phosphorylation. Although concentrations of sorafenib required for the antitumor effect in therapy-resistant sublines were higher than those needed in parental cells, the drug showed efficacy in cells which became resistant to bicalutamide and docetaxel respectively. Most interestingly, we show that sorafenib has an inhibitory effect on androgen receptor (AR) and prostate-specific antigen expression. In cells in which AR expression was downregulated by short interfering RNA, the treatment with sorafenib increased apoptosis in an additive manner. In summary, the results of the present study indicate that there is a potential to use sorafenib in prostate cancers as an adjuvant therapy option to current androgen ablation treatments, but also in progressed prostate cancers that become unresponsive to standard therapies

The node of Ranvier in CNS pathology.

Healthy nodes of Ranvier are crucial for action potential propagation along myelinated axons, both in the central and in the peripheral nervous system. Surprisingly, the node of Ranvier has often been neglected when describing CNS disorders, with most pathologies classified simply as being due to neuronal defects in the grey matter or due to oligodendrocyte damage in the white matter. However, recent studies have highlighted changes that occur in pathological conditions at the node of Ranvier, and at the associated paranodal and juxtaparanodal regions where neurons and myelinating glial cells interact. Lengthening of the node of Ranvier, failure of the electrically resistive seal between the myelin and the axon at the paranode, and retraction of myelin to expose voltage-gated K(+) channels in the juxtaparanode, may contribute to altering the function of myelinated axons in a wide range of diseases, including stroke, spinal cord injury and multiple sclerosis. Here, we review the principles by which the node of Ranvier operates and its molecular structure, and thus explain how defects at the node and paranode contribute to neurological disorders

Components of gait in people with and without mild cognitive impairment

Background: Several objective gait parameters are associated with cognitive impairment, but there is limitedknowledge of gait models in people with mild cognitive impairment (MCI).Research question: How can 18 objective gait characteristics be used to define different components of gait inpeople with MCI (with suspected incipient neurocognitive disorder) and cognitively unimpaired people (CU),respectively?Methods: Spatiotemporal gait data were collected by using an electronic walkway (GAITRite®), i.e. assessmentsin comfortable gait speed. Using cross-sectional gait data, two principal component analyses (PCA) were performed(varimax rotation) to define different components of gait in people with MCI (n = 114) and CU (n = 219),respectively, from the BioFINDER-2 study.Results: Both PCAs produced four components, here called Variability, Pace/Stability, Rhythm and Asymmetry.Total variance explained was 81.0% (MCI) versus 80.3% (CU). The Variability component explained the largestamount of variance (about 25%) in both groups. The highest loading gait parameter was the same for bothgroups in three out of four components, i.e. step velocity variability (Variability), mean step length (Pace/Stability)and mean step time (Rhythm). In the asymmetry component, stance time asymmetry (MCI) and swingtime asymmetry (CU) loaded the highest.Significance: The gait components seem similar in people with and without MCI, although there were somedifferences. This study may aid the identification of gait variables that represent different components of gait.Gait parameters such as step velocity variability, mean step length, mean step time as well as swing and stancetime asymmetry could serve as interesting core variables of different gait components in future research in peoplewith MCI (with suspected incipient neurocognitive disorder) and CU. However, the selection of gait variablesdepends on the purpose. It needs to be noted that assessment of variability measures requires more advancedtechnology than is usually used in the clinic