Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Effects of ecosystem protection on scallop populations within a community-led temperate marine reserve

This study investigated the effects of a newly established, fully protected marine reserve on benthic habitats and two commercially valuable species of scallop in Lamlash Bay, Isle of Arran, United Kingdom. Annual dive surveys from 2010 to 2013 showed the abundance of juvenile scallops to be significantly greater within the marine reserve than outside. Generalised linear models revealed this trend to be significantly related to the greater presence of macroalgae and hydroids growing within the boundaries of the reserve. These results suggest that structurally complex habitats growing within the reserve have substantially increased spat settlement and/or survival. The density of adult king scallops declined threefold with increasing distance from the boundaries of the reserve, indicating possible evidence of spillover or reduced fishing effort directly outside and around the marine reserve. However, there was no difference in the mean density of adult scallops between the reserve and outside. Finally, the mean age, size, and reproductive and exploitable biomass of king scallops were all significantly greater within the reserve. In contrast to king scallops, the population dynamics of queen scallops (Aequipecten opercularis) fluctuated randomly over the survey period and showed little difference between the reserve and outside. Overall, this study is consistent with the hypothesis that marine reserves can encourage the recovery of seafloor habitats, which, in turn, can benefit populations of commercially exploited species, emphasising the importance of marine reserves in the ecosystem-based management of fisheries

The Neurotrophic Receptor Ntrk2 Directs Lymphoid Tissue Neovascularization during Leishmania donovani Infection

The neurotrophic tyrosine kinase receptor type 2 (Ntrk2, also known as TrkB) and its ligands brain derived neurotrophic factor (Bdnf), neurotrophin-4 (NT-4/5), and neurotrophin-3 (NT-3) are known primarily for their multiple effects on neuronal differentiation and survival. Here, we provide evidence that Ntrk2 plays a role in the pathologic remodeling of the spleen that accompanies chronic infection. We show that in Leishmania donovani-infected mice, Ntrk2 is aberrantly expressed on splenic endothelial cells and that new maturing blood vessels within the white pulp are intimately associated with F4/80hiCD11bloCD11c+ macrophages that express Bdnf and NT-4/5 and have pro-angiogenic potential in vitro. Furthermore, administration of the small molecule Ntrk2 antagonist ANA-12 to infected mice significantly inhibited white pulp neovascularization but had no effect on red pulp vascular remodeling. We believe this to be the first evidence of the Ntrk2/neurotrophin pathway driving pathogen-induced vascular remodeling in lymphoid tissue. These studies highlight the therapeutic potential of modulating this pathway to inhibit pathological angiogenesis

Low Plasma Vitamin D (25-Hydroxycholecalciferol) in Children and Adolescents Diagnosed with Cancer: A Case-Control Study

Introduction: Children and young people with cancer are less likely to spend time outdoors and they may also have a limited dietary intake. In addition, some cancer treatments can increase vitamin D catabolism. Objectives: This study aimed to investigate if there was an increased risk of poor vitamin D status in newly diagnosed childhood cancer patients compared to healthy controls in Scotland. Methods: Plasma 25 (OH) D was measured in children and adolescents during initial cancer treatment and compared to 33 healthy controls. Vitamin D deficiency was classified as plasma 25 (OH) D <25 nmol/l, with a plasma 25 (OH) D of 25-49 nmol/l classified as insufficient. Results: Forty-one patients (median age 3.8 years, IQR 1.9-8.0) were diagnosed with cancer, 63% were male. Twenty-three (56 %) had solid tumours, 18 (44%) had haematological cancers. Median (IQR) plasma 25 (OH) D at recruitment was 37.0 nmol/l (23.7-58.2). Ten patients (24%) had vitamin D deficiency and 17 (41%) patients were classified as insufficient. The median (IQR) plasma 25 (OH) D in the control group (n = 33) was 37.5 nmol/l (29.0-58.0). Six controls (18%) had vitamin D deficiency and 14 (42%) were classified as having insufficient results. Plasma 25 (OH) D did not differ (p > 0.05) between the patients and the controls. Conclusions: Almost three in four Scottish children treated for cancer had vitamin D deficiency or insufficiency; there was no increased risk of poor vitamin D status compared to healthy controls. Assessment of vitamin D status at diagnosis and in response to the course of treatment appears necessary to optimise nutritional management.sch_dieThe determinants of nutritional risk in children and young people with cancer3pub4423pub

The Extrachromosomal EAST Protein of Drosophila Can Associate with Polytene Chromosomes and Regulate Gene Expression

The EAST protein of Drosophila is a component of an expandable extrachromosomal domain of the nucleus. To better understand its function, we studied the dynamics and localization of GFP-tagged EAST. In live larval salivary glands, EAST-GFP is highly mobile and localizes to the extrachromosomal nucleoplasm. When these cells are permeabilized, EAST-GFP rapidly associated with polytene chromosomes. The affinity to chromatin increases and mobility decreases with decreasing salt concentration. Deleting the C-terminal residues 1535 to 2301 of EAST strongly reduces the affinity to polytene chromosomes. The bulk of EAST-GFP co-localizes with heterochromatin and is absent from transcriptionally active chromosomal regions. The predominantly chromosomal localization of EAST-GFP can be detected in non-detergent treated salivary glands of pupae as they undergo apoptosis, however not in earlier stages of development. Consistent with this chromosomal pattern of localization, genetic evidence indicates a role for EAST in the repression of gene expression, since a lethal east mutation is allelic to the viable mutation suppressor of white-spotted. We propose that EAST acts as an ion sensor that modulates gene expression in response to changing intracellular ion concentrations

Rheumatoid arthritis patients receive less frequent acute reperfusion and secondary prevention therapy after myocardial infarction compared with the general population

INTRODUCTION: The 30-day case-fatality rate after acute myocardial infarction (MI) for rheumatoid arthritis (RA) patients is twice that of the general population. This study compared the frequency and timeliness of early reperfusion therapy and treatment with secondary prevention medications after acute MI in RA patients and controls. METHODS: We performed a structured medical chart review of RA patients and matched controls who had been admitted with acute MI to one of three hospitals in Victoria, Australia, between 1995 and 2005. The administration and timing of acute reperfusion therapy and in-hospital treatment with secondary prevention medications were compared between the two groups. Acute reperfusion was defined as thrombolysis or percutaneous coronary intervention (PCI) within 12 hours of the first symptom of MI. RESULTS: The medical charts of 90 RA patients and 90 matched controls were reviewed. The RA patients were significantly less likely to receive acute reperfusion compared with the controls (16% versus 37%: odds ratio (OR), 0.27; 95% confidence interval (CI), 0.10 to 0.64)), and this difference persisted after adjusting for type of MI, clinical setting of MI, and prior MI (OR, 0.2; 95% CI, 0.05 to 0.6). The RA patients also received less-frequent in-hospital treatment with beta blockers (71% versus 83%; OR, 0.42; 95% CI, 0.18 to 0.96) and lipid-lowering agents (40% versus 70%; OR, 0.21; 95% CI, 0.09 to 0.46). CONCLUSIONS: RA patients who experience acute MI receive acute reperfusion and secondary prevention medications less frequently than do controls. This may contribute to higher case-fatality rates after MI in RA patients

Sternalis muscle: an underestimated anterior chest wall anatomical variant

Over the recent years, an increased alertness for thorough knowledge of anatomical variants with clinical significance has been recorded in order to minimize the risks of surgical complications. We report a rare case of bilateral strap-like sternalis muscle of the anterior chest wall in a female cadaver. Its presence may evoke alterations in the electrocardiogram or confuse a routine mammography. The incidental finding of a sternalis muscle in mammography, CT, and MRI studies must be documented in a patient's medical records as it can be used as a pedicle flap or flap microvascular anastomosis during reconstructive surgery of the anterior chest wall, head and neck, and breast. Moreover, its presence may be misdiagnosed as a wide range of benign and malignant anterior chest wall lesions and tumors

MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are non-coding RNA molecules that posttranscriptionally regulate expression of target genes and have been implicated in the progress of cancer proliferation, differentiation and apoptosis. The aim of this study was to determine whether microRNA-21 (miR-21), a specific microRNA implicated in multiple aspects of carcinogenesis, impacts breast cancer invasion by regulating the tissue inhibitor of metalloproteinase 3 (TIMP3) gene.</p> <p>Methods</p> <p>miR-21 expression was investigated in 32 matched breast cancer and normal breast tissues, and in four human breast cancer cell lines, by Taqman quantitative real-time PCR. Cell invasive ability was determined by matrigel invasion assay in vitro, in cells transfected with miR-21 or anti-miR-21 oligonucleotides. In addition, the regulation of tissue inhibitor of metalloproteinase 3 (TIMP3) by miR-21 was evaluated by western blotting and luciferase assays.</p> <p>Results</p> <p>Of the 32 paired samples analyzed, 25 breast cancer tissues displayed overexpression of miR-21 in comparison with matched normal breast epithelium. Additionally, incidence of lymph node metastasis closely correlated with miR-21 expression, suggesting a role for miR-21 in metastasis. Similarly, each of the four breast cancer cell lines analyzed overexpressed miR-21, to varied levels. Further, cells transfected with miR-21 showed significantly increased matrigel invasion compared with control cells, whereas transfection with anti-miR-21 significantly decreased cell invasion. Evaluation of TIMP3 protein levels, a peptidase involved in extarcellular matrix degredation, inversely correlated with miR-21 expression.</p> <p>Conclusion</p> <p>As knockdown of miR-21 increased TIMP3 protein expression and luciferase reporter activity, our data suggests that miR-21 could promote invasion in breast cancer cells via its regulation of TIMP3.</p

Nutrition education: a questionnaire for assessment and teaching

It is generally recognized that there is a need for improved teaching of nutrition in medical schools and for increased education of the general population. A questionnaire, derived in part from a study of physician knowledge, was administered to first year medical students in order to assess their knowledge of various aspects of nutrition and metabolism, and as a teaching tool to transmit information about the subject. The performance of first year students was consistent with a generally educated population but there were surprising deficits in some fundamental areas of nutrition. Results of the questionnaire are informative about student knowledge, and immediate reinforcement from a questionnaire may provide a useful teaching tool. In addition, some of the subject matter can serve as a springboard for discussion of critical issues in nutrition such as obesity and markers for cardiovascular disease. A major barrier to improved teaching of nutrition is the lack of agreement on some of these critical issues and there are apparent inconsistencies in recommendations of government and health agencies. It seems reasonable that improved teaching should address the lack of knowledge of nutrition, rather than knowledge of official guidelines. Student awareness of factual information should be the primary goal