Sub-chronic ketamine administration increases dopamine synthesis capacity in the mouse midbrain: a preclinical in vivo PET study

PURPOSE: There is robust evidence that people with schizophrenia show elevated dopamine (DA) synthesis capacity in the striatum. This finding comes from positron emission tomography (PET) studies using radiolabelled l-3,4-dihydroxyphenylalanine (18F-DOPA). DA synthesis capacity also appears to be elevated in the midbrain of people with schizophrenia compared to healthy controls. We therefore aimed to optimise a method to quantify 18F-DOPA uptake in the midbrain of mice, and to utilise this method to quantify DA synthesis capacity in the midbrain of the sub-chronic ketamine model of schizophrenia-relevant hyperdopaminergia. PROCEDURES: Adult male C57Bl6 mice were treated daily with either ketamine (30 mg/kg, i.p.) or vehicle (saline) for 5 days. On day 7, animals were administered 18F-DOPA (i.p.) and scanned in an Inveon PET/CT scanner. Data from the saline-treated group were used to optimise an atlas-based template to position the midbrain region of interest and to determine the analysis parameters which resulted in the greatest intra-group consistency. These parameters were then used to compare midbrain DA synthesis capacity (KiMod) between ketamine- and saline-treated animals. RESULTS: Using an atlas-based template to position the 3.7 mm3 midbrain ROI with a T*-Tend window of 15-140 min to estimate KiMod resulted in the lowest intra-group variability and moderate test-retest agreement. Using these parameters, we found that KiMod was elevated in the midbrain of ketamine-treated animals in comparison to saline-treated animals (t(22) = 2.19, p = 0.048). A positive correlation between DA synthesis capacity in the striatum and the midbrain was also evident in the saline-treated animals (r2 = 0.59, p = 0.005) but was absent in ketamine-treated animals (r2 = 0.004, p = 0.83). CONCLUSIONS: Using this optimised method for quantifying 18F-DOPA uptake in the midbrain, we found that elevated striatal DA synthesis capacity in the sub-chronic ketamine model extends to the midbrain. Interestingly, the dysconnectivity between the midbrain and striatum seen in this model is also evident in the clinical population. This model may therefore be ideal for assessing novel compounds which are designed to modulate pre-synaptic DA synthesis capacity

'Write when it hurts. Then write till it doesn't': athlete voice and the lived realities of one female professional athlete

Digital media has played a central role in promoting women’s sport, where female athletes are increasingly using online platforms to control their own representations and challenge male dominated sporting institutions. Alternatively, some commentators claim that female athletes’ use of digital media contributes to patriarchal practices in sport, where through self-promotion and image building they do little to advance representations of women’s sport. This paper interrogates these ideas, adopting a postfeminist sensibility and collaborative research approach to examine the online self-representations of a female athlete and blogger. The athlete in question is Meghan MacLaren, a professional golfer on the Ladies’ European Tour who documents her life as a professional athlete through her online blog. Primarily, the authors present a critical analysis of MacLaren’s blog posts over a period of three years, from MacLaren turning professional to the present day. This initial analysis prompted a series of questions around MacLaren’s blogging and self-representations, which the authors then posed directly to her, and Meghan was invited to respond in her own voice. Using a collaborative approach with MacLaren as co-author, this paper seeks to draw attention to the diverging realities of a female professional athlete fulfilling dichotomous identities as a simultaneously trusting and doubting golf performer on the course and a self-appointed athlete activist online, all the while operating in, and influenced by the patriarchal and capitalist cultural environment of golf

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Study of the impact of ice formation in leads upon the sea ice pack mass balance using a new frazil and grease ice parameterization

Leads are cracks in sea ice that often form because of deformation. During winter months, leads expose the ocean to the cold atmosphere, resulting in supercooling and the formation of frazil ice crystals within the mixed layer. Here the authors investigate the role of frazil ice formation in leads on the mass balance of the sea ice pack through the incorporation of a new module into the Los Alamos sea ice model (CICE). The frazil ice module considers an initial cooling of leads followed by a steady-state formation of uniformly distributed single size frazil ice crystals that precipitate to the ocean surface as grease ice. The grease ice is pushed against one of the lead edges by wind and water drag that the authors represent through a variable collection thickness for new sea ice. Simulations of the sea ice cover in the Arctic and Antarctic are performed and compared to a model that treats leads the same as the open ocean. The processes of ice formation in the new module slow down the refreezing of leads, resulting in a longer period of frazil ice production. The fraction of frazil-derived sea ice increases from 10% to 50%, corresponding better to observations. The new module has higher ice formation rates in areas of high ice concentration and thus has a greater impact within multiyear ice than it does in the marginal seas. The thickness of sea ice in the central Arctic increases by over 0.5 m, whereas within the Antarctic it remains unchanged

Reactive oxygen species in phagocytic leukocytes

Phagocytic leukocytes consume oxygen and generate reactive oxygen species in response to appropriate stimuli. The phagocyte NADPH oxidase, a multiprotein complex, existing in the dissociated state in resting cells becomes assembled into the functional oxidase complex upon stimulation and then generates superoxide anions. Biochemical aspects of the NADPH oxidase are briefly discussed in this review; however, the major focus relates to the contributions of various modes of microscopy to our understanding of the NADPH oxidase and the cell biology of phagocytic leukocytes

Clinical predictors of lacunar syndrome not due to lacunar infarction

Background: Lacunar syndrome not due to lacunar infarct is poorly characterised. This single centre, retrospective study was conducted to describe the clinical characteristics of patients with lacunar syndrome not due to lacunar infarct and to identify clinical predictors of this variant of lacunar stroke. Methods: A total of 146 patients with lacunar syndrome not due to lacunar infarction were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986-2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 146 patients with lacunar syndrome not due to lacunar infarct were compared with those of the 733 patients with lacunar infarction. Results: Lacunar syndrome not due to lacunar infarct accounted for 16.6% (146/879) of all cases of lacunar stroke. Subtypes of lacunar syndromes included pure motor stroke in 63 patients, sensorimotor stroke in 51, pure sensory stroke in 14, atypical lacunar syndrome in 9, ataxic hemiparesis in 5 and dysarthria-clumsy hand in 4. Valvular heart disease, atrial fibrillation, sudden onset, limb weakness and sensory symptoms were significantly more frequent among patients with lacunar syndrome not due to lacunar infarct than in those with lacunar infarction, whereas diabetes was less frequent. In the multivariate analysis, atrial fibrillation (OR = 4.62), sensorimotor stroke (OR = 4.05), limb weakness (OR = 2.09), sudden onset (OR = 2.06) and age (OR = 0.96) were independent predictors of lacunar syndrome not due to lacunar infarct. Conclusions: Although lacunar syndromes are highly suggestive of small deep cerebral infarctions, lacunar syndromes not due to lacunar infarcts are found in 16.6% of cases. The presence of sensorimotor stroke, limb weakness and sudden onset in a patient with atrial fibrillation should alert the clinician to the possibility of a lacunar syndrome not due to a lacunar infarct