413 research outputs found
Cancer and systemic inflammation: treat the tumour and treat the host
Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease
The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer
Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer
Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions
Improvements in sequencing technologies and reduced experimental costs have
resulted in a vast number of studies generating high-throughput data. Although
the number of methods to analyze these "omics" data has also increased,
computational complexity and lack of documentation hinder researchers from
analyzing their high-throughput data to its true potential. In this chapter we
detail our data-driven, transkingdom network (TransNet) analysis protocol to
integrate and interrogate multi-omics data. This systems biology approach has
allowed us to successfully identify important causal relationships between
different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of
data
Extending ontological categorization through a dual process conceptual architecture
In this work we present a hybrid knowledge representation system aiming at extending the representational and reasoning capabilities of classical ontologies by taking into account the theories of typicality in conceptual processing. The system adopts a categorization process inspired to the dual process theories and, from a representational perspective, is equipped with a heterogeneous knowledge base that couples conceptual spaces and ontological formalisms. The system has been experimentally assessed in a conceptual categorization task where common sense linguistic descriptions were given in input, and the corresponding target concepts had to be identified. The results show that the proposed solution substantially improves the representational and reasoning \ue2\u80\u9cconceptual\ue2\u80\u9d capabilities of standard ontology-based systems
Subliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula:a meta-analysis of fMRI studies
Background: Non-conscious neural activation may underlie various psychological functions in health and disorder. However, the neural substrates of non-conscious processing have not been entirely elucidated. Examining the differential effects of arousing stimuli that are consciously, versus unconsciously perceived will improve our knowledge of neural circuitry involved in non-conscious perception. Here we conduct preliminary analyses of neural activation in studies that have used both subliminal and supraliminal presentation of the same stimulus. Methods: We use Activation Likelihood Estimation (ALE) to examine functional Magnetic Resonance Imaging (fMRI) studies that uniquely present the same stimuli subliminally and supraliminally to healthy participants during functional magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies representing subliminal stimulation and 315 foci from 10 studies representing supraliminal stimulation. Results: The anterior cingulate cortex is significantly activated during both subliminal and supraliminal stimulus presentation. Subliminal stimuli are linked to significantly increased activation in the right fusiform gyrus and right insula. Supraliminal stimuli show significantly increased activation in the left rostral anterior cingulate. Conclusions: Non-conscious processing of arousing stimuli may involve primary visual areas and may also recruit the insula, a brain area involved in eventual interoceptive awareness. The anterior cingulate is perhaps a key brain region for the integration of conscious and non-conscious processing. These preliminary data provide candidate brain regions for further study in to the neural correlates of conscious experience
Critical Role of NADPH Oxidase in Neuronal Oxidative Damage and Microglia Activation following Traumatic Brain Injury
BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS) following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2)(-)), and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2)(-) induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI
The Timing of the Cognitive Cycle
We propose that human cognition consists of cascading cycles of recurring brain
events. Each cognitive cycle senses the current situation, interprets it with
reference to ongoing goals, and then selects an internal or external action in
response. While most aspects of the cognitive cycle are unconscious, each cycle
also yields a momentary “ignition” of conscious broadcasting.
Neuroscientists have independently proposed ideas similar to the cognitive
cycle, the fundamental hypothesis of the LIDA model of cognition. High-level
cognition, such as deliberation, planning, etc., is typically enabled by
multiple cognitive cycles. In this paper we describe a timing model LIDA's
cognitive cycle. Based on empirical and simulation data we propose that an
initial phase of perception (stimulus recognition) occurs 80–100 ms from
stimulus onset under optimal conditions. It is followed by a conscious episode
(broadcast) 200–280 ms after stimulus onset, and an action selection phase
60–110 ms from the start of the conscious phase. One cognitive cycle would
therefore take 260–390 ms. The LIDA timing model is consistent with brain
evidence indicating a fundamental role for a theta-gamma wave, spreading forward
from sensory cortices to rostral corticothalamic regions. This posteriofrontal
theta-gamma wave may be experienced as a conscious perceptual event starting at
200–280 ms post stimulus. The action selection component of the cycle is
proposed to involve frontal, striatal and cerebellar regions. Thus the cycle is
inherently recurrent, as the anatomy of the thalamocortical system suggests. The
LIDA model fits a large body of cognitive and neuroscientific evidence. Finally,
we describe two LIDA-based software agents: the LIDA Reaction Time agent that
simulates human performance in a simple reaction time task, and the LIDA Allport
agent which models phenomenal simultaneity within timeframes comparable to human
subjects. While there are many models of reaction time performance, these
results fall naturally out of a biologically and computationally plausible
cognitive architecture
Resting-State Functional Connectivity between Fronto-Parietal and Default Mode Networks in Obsessive-Compulsive Disorder
Background: Obsessive-compulsive disorder (OCD) is characterized by an excessive focus on upsetting or disturbing thoughts, feelings, and images that are internally-generated. Internally-focused thought processes are subserved by the ‘‘default mode network’ ’ (DMN), which has been found to be hyperactive in OCD during cognitive tasks. In healthy individuals, disengagement from internally-focused thought processes may rely on interactions between DMN and a frontoparietal network (FPN) associated with external attention and task execution. Altered connectivity between FPN and DMN may contribute to the dysfunctional behavior and brain activity found in OCD. Methods: The current study examined interactions between FPN and DMN during rest in 30 patients with OCD (17 unmedicated) and 32 control subjects (17 unmedicated). Timecourses from seven fronto-parietal seeds were correlated across the whole brain and compared between groups. Results: OCD patients exhibited altered connectivity between FPN seeds (primarily anterior insula) and several regions of DMN including posterior cingulate cortex, medial frontal cortex, posterior inferior parietal lobule, and parahippocampus. These differences were driven largely by a reduction of negative correlations among patients compared to controls. Patients also showed greater positive connectivity between FPN and regions outside DMN, including thalamus, lateral frontal cortex, and somatosensory/motor regions
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