178 research outputs found
Development of cavernous haemangioma following radical chemo-radiotherapy for nasopharyngeal carcinoma
Objective: We report an adult case of nasopharyngeal carcinoma treated with radical chemo-radiotherapy, with subsequent development of a histologically proved temporal cavernous haemangioma within the radiation field. Method: Case report and review of the current literature concerning radiation-induced, secondary, space-occupying lesions. Conclusion: The increasing role of radiotherapy in nasopharyngeal carcinoma treatment, together with improved patient survival, is likely to lead to radiation-induced, secondary, space-occupying lesions being encountered more frequently. We emphasise the need to be vigilant for this important but relatively rare complication, which has significant associated morbidity
Tumor Necrosis Factor α Inhibits Expression of the Iron Regulating Hormone Hepcidin in Murine Models of Innate Colitis
Background: Abnormal expression of the liver peptide hormone hepcidin, a key regulator of iron homeostasis, contributes to the pathogenesis of anemia in conditions such as inflammatory bowel disease (IBD). Since little is known about the mechanisms that control hepcidin expression during states of intestinal inflammation, we sought to shed light on this issue using mouse models. Methodology/Principal Findings: Hepcidin expression was evaluated in two types of intestinal inflammation caused by innate immune activation—dextran sulfate sodium (DSS)-induced colitis in wild-type mice and the spontaneous colitis occurring in T-bet/Rag2-deficient (TRUC) mice. The role of tumor necrosis factor (TNF) was investigated by in vivo neutralization, and by treatment of a hepatocyte cell line, as well as mice, with the recombinant cytokine. Expression and activation of Smad1, a positive regulator of hepcidin transcription, were assessed during colitis and following administration or neutralization of TNF. Hepcidin expression progressively decreased with time during DSS colitis, correlating with changes in systemic iron distribution. TNF inhibited hepcidin expression in cultured hepatocytes and non-colitic mice, while TNF neutralization during DSS colitis increased it. Similar results were obtained in TRUC mice. These effects involved a TNF-dependent decrease in Smad1 protein but not mRNA. Conclusions/Significance: TNF inhibits hepcidin expression in two distinct types of innate colitis, with down-regulation of Smad1 protein playing an important role in this process. This inhibitory effect of TNF may be superseded by other factors in the context of T cell-mediated colitis given that in the latter form of intestinal inflammation hepcidin is usually up-regulated
Low level constraints on dynamic contour path integration
Contour integration is a fundamental visual process. The constraints on integrating
discrete contour elements and the associated neural mechanisms have typically been
investigated using static contour paths. However, in our dynamic natural environment
objects and scenes vary over space and time. With the aim of investigating the
parameters affecting spatiotemporal contour path integration, we measured human
contrast detection performance of a briefly presented foveal target embedded in
dynamic collinear stimulus sequences (comprising five short 'predictor' bars appearing
consecutively towards the fovea, followed by the 'target' bar) in four experiments. The
data showed that participants' target detection performance was relatively unchanged
when individual contour elements were separated by up to 2° spatial gap or 200ms
temporal gap. Randomising the luminance contrast or colour of the predictors, on the
other hand, had similar detrimental effect on grouping dynamic contour path and
subsequent target detection performance. Randomising the orientation of the
predictors reduced target detection performance greater than introducing misalignment
relative to the contour path. The results suggest that the visual system integrates
dynamic path elements to bias target detection even when the continuity of path is
disrupted in terms of spatial (2°), temporal (200ms), colour (over 10 colours) and
luminance (-25% to 25%) information. We discuss how the findings can be largely
reconciled within the functioning of V1 horizontal connections
A Glucose Fuel Cell for Implantable Brain–Machine Interfaces
We have developed an implantable fuel cell that generates power through glucose oxidation, producing steady-state power and up to peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain–machine interfaces can thus potentially benefit from having their implanted units powered or recharged by glucose fuel cells
Women's gambling behaviour, product preferences, and perceptions of product harm: Differences by age and gambling risk status
Background: Women's participation in, and harm from gambling, is steadily increasing. There has been very limited research to investigate how gambling behaviour, product preferences, and perceptions of gambling harm may vary across subgroups of women. Methods: This study surveyed a convenience sample of 509 women from Victoria and New South Wales, Australia. Women were asked a range of questions about their socio-demographic characteristics and gambling behaviour. Focusing on four gambling products in Australia-casino gambling, electronic gambling machines (EGMs), horse betting, and sports betting-women were asked about their frequency of participation, their product preferences, and perceptions of product harms. The sample was segmented a priori according to age and gambling risk status, and differences between groups were identified using Chi-square tests and ANOVAs. Thematic analysis was used to interpret qualitative data. Results: Almost two thirds (n=324, 63.7%) of women had engaged with one of the four products in the previous 12 months. Compared to other age groups, younger women aged 16-34 years exhibited a higher proportion of problem gambling, gambled more frequently, and across more products. While EGMs were the product gambled on most frequently by women overall, younger women were significantly more likely to bet on sports and gamble at casinos relative to older women. Qualitative data indicated that younger women engaged with gambling products as part of a 'night out', 'with friends', due to their 'ease of access' and perceived 'chance of winning big'. There were significant differences in the perceptions of the harms associated with horse and sports betting according to age and gambling risk status, with younger women and gamblers perceiving these products as less harmful. Conclusions: This study highlights that there are clear differences in the gambling behaviour, product preferences, and perceptions of product harms between subgroups of women. A gendered approach will enable public health researchers and policymakers to ensure that the unique factors associated with women's gambling are taken into consideration in a comprehensive public health approach to reducing and preventing gambling harm
The Impact of Acute Psychosocial Stress on Magnetoencephalographic Correlates of Emotional Attention and Exogenous Visual Attention
Stress-induced acute activation of the cerebral catecholaminergic systems has often been found in rodents. However, little is known regarding the consequences of this activation on higher cognitive functions in humans. Theoretical inferences would suggest increased distractibility in the sense of increased exogenous attention and emotional attention. The present study investigated the influence of acute stress responses on magnetoencephalographic (MEG) correlates of visual attention. Healthy male subjects were presented emotional and neutral pictures in three subsequent MEG recording sessions after being exposed to a TSST-like social stressor, intended to trigger a HPA-response. The subjects anticipation of another follow-up stressor was designed to sustain the short-lived central catecholaminergic stress reactions throughout the ongoing MEG recordings. The heart rate indicates a stable level of anticipatory stress during this time span, subsequent cortisol concentrations and self-report measures of stress were increased. With regard to the MEG correlates of attentional functions, we found that the N1m amplitude remained constantly elevated during stressor anticipation. The magnetic early posterior negativity (EPNm) was present but, surprisingly, was not at all modulated during stressor anticipation. This suggests that a general increase of the influence of exogenous attention but no specific effect regarding emotional attention in this time interval. Regarding the time course of the effects, an influence of the HPA on these MEG correlates of attention seems less likely. An influence of cerebral catecholaminergic systems is plausible, but not definite
Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson\u27s disease study
\ua9 The Author(s) 2024. Estimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson’s disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9
7 10−34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1
7 10−35). Female patients were 22% more likely to have a positive PDGT (P = 3
7 10−4), and for individuals with FH+ this likelihood was 55% higher (P = 1
7 10−14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD
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