56 research outputs found
Exonic DNA Sequencing of ERBB4 in Bipolar Disorder
The Neuregulin-ErbB4 pathway plays a crucial role in brain development and
constitutes one of the most biologically plausible signaling pathways implicated
in schizophrenia and, to a lesser extent, in bipolar disorder (BP). However,
recent genome-wide association analyses have not provided evidence for common
variation in NRG1 or ERBB4 influencing
schizophrenia or bipolar disorder susceptibility. In this study, we investigate
the role of rare coding variants in ERBB4 in BP cases with
mood-incongruent psychotic features, a form of BP with arguably the greatest
phenotypic overlap with schizophrenia. We performed Sanger sequencing of all 28
exons in ERBB4, as well as part of the promoter and part of the
3′UTR sequence, hypothesizing that rare deleterious variants would be
found in 188 cases with mood-incongruent psychosis from the GAIN BP study. We
found 42 variants, of which 16 were novel, although none were non-synonymous or
clearly deleterious. One of the novel variants, present in 11.2% of
cases, is located next to an alternative stop codon, which is associated with a
shortened transcript of ERBB4 that is not translated. We
genotyped this variant in the GAIN BP case-control samples and found a
marginally significant association with mood-incongruent psychotic BP compared
with controls (additive model: OR = 1.64,
P-value = 0.055; dominant model:
OR = 1.73.
P-value = 0.039). In
conclusion, we found no rare variants of clear deleterious effect, but did
uncover a modestly associated novel variant that could affect alternative
splicing of ERBB4. However, the modest sample size in this
study cannot definitively rule out a role for rare variants in bipolar disorder
and studies with larger sample sizes are needed to confirm the observed
association
Exploring new physics frontiers through numerical relativity
The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology
A pilot study of normobaric oxygen therapy in acute ischemic stroke
BACKGROUND AND PURPOSE:Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke.
METHODS:We randomized patients with acute stroke (<12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups.
RESULTS:Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (+/-SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8+/-22% versus 149.1+/-41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6).
CONCLUSIONS:High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy
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