PET and SPECT Imaging in Hyperkinetic Movement Disorders

Movement disorders can be classified in hypokinetic (e.g., Parkinson's disease, PD) and hyperkinetic disorders (e.g., dystonia, chorea, tremor, tics, myoclonus, and restless legs syndrome). In this chapter, we will discuss results from positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging studies in patients with tremor, tics, myoclonus, and restless legs syndrome. Most studies in patients with tremor included patients with essential tremor (ET): a bilateral, largely symmetric, postural or kinetic tremor mainly involving the upper limbs and sometimes the head. Other studies evaluated patients with orthostatic tremor (OT): an unusually high frequent tremor in the legs that mainly occurs when patients are standing still. Increased regional cerebral blood flow (rCBF) and increased glucose metabolism have been found in the cerebellum, sensorimotor cortex, and thalamus in both patients with ET and OT compared to controls. Both PET and SPECT studies have evaluated the dopamine system in patients with ET and OT. Most imaging studies in patients with ET showed no, or only subtle loss of striatal tracer binding to the dopamine transporter indicating that ET is not characterized by nigrostriatal cell loss. The serotonin and/or gamma-aminobutyric acid (GABA) systems may play a role in the pathophysiology of ET. PET and SPECT imaging of the dopamine and serotonin system in patients with OT showed no abnormalities. Tics, the clinical hallmark of Gilles de la Tourette syndrome (TS), are relatively brief and intermittent involuntary movements (motor tic) and sounds (phonic tic). The essential features of tics are that (1) they can be temporarily suppressed; after suppression a rebound usually occurs with a flurry of tics; (2) the patient experiences an urge to tic, and (3) the tic is followed by a short moment of relief. Using 18F-FDG PET, it was shown that TS is a network disorder where multiple brain areas are active or inactive at the same time. The exact composition of this network is yet to be determined. Using rCBF PET and SPECT many brain regions were found to be abnormal, however, tics mostly correlated with hypoperfusion of the caudate nucleus and cingulate cortex. Both dopamine and serotonin are likely to play a role in the pathophysiology of TS. It is hypothesized that TS is characterized by low serotonin levels that modulate increased phasic dopamine release. Myoclonus is defined as a brief muscle jerk and occurs in many neurologic and non-neurologic disorders. Imaging with PET and SPECT in patients with myoclonus mainly showed abnormalities consistent with the underlying disorder. We described PET and SPECT imaging results in patients in which myoclonus was a prominent symptom. Hypoperfusion and/or hypometabolism of the frontoparietal cortex was found in patients with negative epileptic myoclonus, Alzheimer's disease, corticobasal degeneration, Creutzfeldt-Jakob disease, fatal familiar insomnia, and posthypoxic myoclonus. Other findings that were frequently reported were decreased rCBF and/or glucose metabolism in the cerebellum and thalamus and abnormalities in the dopamine system. Restless legs syndrome (RLS) is defined as an urge to move the legs accompanied with an unpleasant sensation in the legs or in another body part that is especially present during the evening and night and that can be accompanied by periodic limb movements in sleep (PLMS). Imaging studies in these patients have mainly focused on the dopamine system. Most PET studies found decreased tracer binding to the dopamine transporter, although this was not found in SPECT studies. Both PET and SPECT studies showed conflicting results regarding dopamine D2/3 receptor binding: both increased and decreased tracer binding was reported. Furthermore, it is likely that the serotonin and opioid systems also play a role in the pathophysiology of RLS.</p

Which facets of mindfulness protect Individuals from the negative experiences of obsessive intrusive thoughts?

Obsessive intrusive thoughts (OITs) are experienced by the majority of the general population, and in their more extreme forms are characteristic of obsessive–compulsive disorder (OCD). These cognitions are said to exist on a continuum that includes differences in their frequency and associated distress. The key factors that contribute to an increased frequency and distress are how the individual appraises and responds to the OIT. Facets of mindfulness, such as nonjudgment and nonreactivity, offer an alternative approach to OITs than the negative appraisals and commonly utilised control strategies that often contribute to distress. Clarifying the role of facets of mindfulness in relation to these cognitions offers a means to elucidate individual characteristics that may offer protection from distress associated with OITs. A sample of nonclinical individuals (n = 583) completed an online survey that assessed their experiences of OITs, including frequency, emotional reaction and appraisals, and trait mindfulness. The findings from a series of multiple regression analyses confirmed that specific facets of mindfulness relating to acting with awareness and acceptance (nonjudgment and nonreactivity) consistently predicted less frequent and distressing experiences of OITs. In contrast, the observe facet emerged as a consistent predictor of negative experiences of OITs. These findings suggest that acting with awareness and acceptance may confer protective characteristics in relation to OITs, but that the observe facet may reflect a hypervigilance to OITs. Mindfulness-based prevention and intervention for OCD should be tailored to take account of the potential differential effects of increasing specific facets of mindfulness

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

Understanding How Microplastics Affect Marine Biota on the Cellular Level Is Important for Assessing Ecosystem Function: A Review

Plastic has become indispensable for human life. When plastic debris is discarded into waterways, these items can interact with organisms. Of particular concern are microscopic plastic particles (microplastics) which are subject to ingestion by several taxa. This review summarizes the results of cutting-edge research about the interactions between a range of aquatic species and microplastics, including effects on biota physiology and secondary ingestion. Uptake pathways via digestive or ventilatory systems are discussed, including (1) the physical penetration of microplastic particles into cellular structures, (2) leaching of chemical additives or adsorbed persistent organic pollutants (POPs), and (3) consequences of bacterial or viral microbiota contamination associated with microplastic ingestion. Following uptake, a number of individual-level effects have been observed, including reduction of feeding activities, reduced growth and reproduction through cellular modifications, and oxidative stress. Microplastic-associated effects on marine biota have become increasingly investigated with growing concerns regarding human health through trophic transfer. We argue that research on the cellular interactions with microplastics provide an understanding of their impact to the organisms’ fitness and, therefore, its ability to sustain their functional role in the ecosystem. The review summarizes information from 236 scientific publications. Of those, only 4.6% extrapolate their research of microplastic intake on individual species to the impact on ecosystem functioning. We emphasize the need for risk evaluation from organismal effects to an ecosystem level to effectively evaluate the effect of microplastic pollution on marine environments. Further studies are encouraged to investigate sublethal effects in the context of environmentally relevant microplastic pollution conditions

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Search for supersymmetry via associated production of charginos and neutralinos in final states with three leptons

A search for associated production of charginos and neutralinos is performed using data recorded with the D0 detector at a p (p) over bar center-of-mass energy of 1.96 TeV at the Fermilab Tevatron Collider. This analysis considers final states with missing transverse energy and three charged leptons, of which at least two are electrons or muons. No evidence for supersymmetry is found in a data set corresponding to an integrated luminosity of 320 pb(-1). Limits on the product of the production cross section and leptonic branching fraction are set. For the minimal supergravity model, a chargino lower mass limit of 117 GeV at the 95% C.L. is derived in regions of parameter space with enhanced leptonic branching fractions