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As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohn's disease led to detection of intestinal m[TNF.sup.+] immune cells during confocal laser endomicroscopy. Patients with high numbers of m[TNF.sup.+] cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of m[TNF.sup.+] cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn's disease and autoimmune or inflammatory disorders., Crohn's disease is characterized by chronic relapsing inflammation of the intestinal mucosa (1), (2). Patients with this incurable disease can suffer from chronic diarrhea, rectal bleeding, abdominal cramping, stenoses and [...]

Rationale Cooling reduced infarct size and improved neurological outcomes in animal studies modeling ischemic stroke, and also improved outcome in randomized clinical trials in patients with hypoxic-ischemic brain injury after cardiac arrest. Cooling awake patients with ischemic stroke has been shown feasible in phase II clinical trials. Primary aim To determine whether systemic cooling to a target body temperature between 34·0 and 35·0°C, started within six-hours of symptom onset and maintained for 24 h, improves functional outcome at three-months in patients with acute ischemic stroke. Design International, multicenter, phase III, randomized, open-label clinical trial with blinded outcome assessment in 1500 patients aged 18 years or older with acute ischemic stroke and a National Institutes of Health Stroke Scale score of 6 up to and including 18. In patients randomized to hypothermia, cooling to a target body temperature of 34-35°C will be started within six-hours after symptom onset with rapid intravenous infusion of refrigerated normal saline or a surface cooling technique and maintained for 24 h with a surface or endovascular technique. Patients randomized to hypothermia will receive pethidine and buspirone to prevent shivering and discomfort. Primary outcome Score on the modified Rankin Scale at 91 days, as analyzed with ordinal logistic regression and expressed as a common odds ratio. Discussion With 750 patients per intervention group, this trial has 90% power to detect 7% absolute improvement at the 5% significance level. The full trial protocol is available at . Identifier: NCT01833312. [ABSTRACT FROM AUTHOR]

In Drosophila polarization sensitivity as revealed in optomotor experiments is mediated by retinula cells R1-6. In the optomotor turning response of the walking fly the response amplitude is a sinusoidal function of E-vector orientation of the stimulus light. For the effect to occur the area of the visual field in which moving vertical stripes are presented must be embedded in an illuminated surround which covers a large part of the visual field. The phase and amplitude of this sinus function do not reflect directly the polarization sensitivity of the photoreceptors mediating it since a) the amplitude is much larger than could be expected from the measured properties of fly retinula cells, b) the effect can be elicited in parts of the visual field viewed by photoreceptors of which half are oriented in mirror symmetry to the other half (equator, frontal area), c) presentation of the stimulus to either eye (at the same height) does not lead to a phase shift in the sinus functions. (A phase shift of 90 ° would be expected in our experiments if the response reflected the fly's bilateral symmetry.) The data suggest that the fly has an 'inner' representation of E-vector orientation. In a closed loop situation in which the fly is illuminated from above by linearly polarized light and is allowed to turn the orientation of the E-vector plane relative to its body axis by its yaw torque it can maintain its optomotor balance (i.e. it can fly straight). Often flies keep their longitudinal body axis roughly parallel or perpendicular to the E-vector plane during the whole experiment (4 min). Flies perform discrete 360 °-loops although the rotating polarizing filter has a 180 ° period. Viewed in the context of the first experiment this observation suggests that the fly, like the bee, evaluates the polarization pattern as a whole and designs its loons accordingly. At least on clear days Drosophila can make use of the polarization pattern of the free sky in flight orientation. Polarization sensitivity is not restricted to the upper part of the eye: Also with the lower part the fly can use a polarization pattern for course control. [ABSTRACT FROM AUTHOR]