Pupillary dynamics reflect the impact of temporal expectation on detection strategy.

Everyday life's perceptual decision-making is informed by experience. In particular, temporal expectation can ease the detection of relevant events in noisy sensory streams. Here, we investigated if humans can extract hidden temporal cues from the occurrences of probabilistic targets and utilize them to inform target detection in a complex acoustic stream. To understand what neural mechanisms implement temporal expectation influence on decision-making, we used pupillometry as a proxy for underlying neuromodulatory activity. We found that participants' detection strategy was influenced by the hidden temporal context and correlated with sound-evoked pupil dilation. A model of urgency fitted on false alarms predicted detection reaction time. Altogether, these findings suggest that temporal expectation informs decision-making and could be implemented through neuromodulatory-mediated urgency signals.

Anti-proliferative and apoptotic effects of Ziziphus Jujube on cervical and breast cancer cells.

OBJECTIVE: Ziziphus Jujube (Jujube) plant has exhibited numerous medicinal and pharmacological properties including antioxidant and anti-inflammatory effects. This study was carried out to investigate its anti-cancer and pro-apoptotic abilities in human cervical and breast cancer cells in vitro. MATERIALS AND METHODS: The cervical OV2008 and breast MCF-7 cancer cells were incubated with different concentrations of Jujube aqueous extraction (0-3 mg/ml) for various times (0-72 h). Cell viability was assessed by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time -PCR analysis. RESULTS: Jujube significantly inhibited cancer cell viability in a dose- and time- dependent manner. Herb-induced apoptosis was associated with enhanced expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent six fold increase in the Bax/Bcl-2 ratio. CONCLUSION: These results indicated that Jujube may be a natural potential and promising agent to prevent or treat human cancers.

Analysis of methylation and mRNA expression status of FADD and FAS genes in patients with oral squamous cell carcinoma

BACKGROUND: Apoptosis is an important mechanism that is responsible for the physiological deletion of harmful, damaged, or unwanted cells. Changed expression of apoptosis-related genes may lead to abnormal cell prolifera tion and finally to tumorigenesis. Our aims were to analyze the promoter methylation and gene expression profiles of FADD and FAS genes in risk of OSCC. MATERIAL AND METHODS: we analyze the promoter methylation status of FADD and FAS genes using Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68 normal oral tissues applied as control. Also, FADD and FAS genes expression were analyzed in 19 cases and 20 normal specimens by Real-Time Reverse- Transcripts PCR. RESULTS: Aberrant promoter methylation of FADD and FAS genes were detected in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively, with a significant difference between cases and healthy controls for both FADD and FAS genes (P<0.001). The gene expression analysis showed statistically significant difference between cases and healthy controls for both FADD (p < 0.02) and FAS (p < 0.007) genes. CONCLUSIONS: To the best our knowledge, the data of this study are the first report regarding, the effect of promoter hypermethylation of the FADD and FAS genes in development of OSCC. To confirm the data, it is recommended doing further study in large sample sizes in various genetic populations

Analysis of methylation and mRNA expression status of FADD and FAS genes in patients with oral squamous cell carcinoma.

BACKGROUND: Apoptosis is an important mechanism that is responsible for the physiological deletion of harmful, damaged, or unwanted cells. Changed expression of apoptosis-related genes may lead to abnormal cell proliferation and finally to tumor genesis. Our aims were to analyze the promoter methylation and gene expression profiles of FADD and FAS genes in risk of OSCC. MATERIAL AND METHODS: we analyze the promoter methylation status of FADD and FAS genes using Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68 normal oral tissues applied as control. Also, FADD and FAS genes expression were analyzed in 19 cases and 20 normal specimens by Real-Time Reverse-Transcripts PCR. RESULTS: Aberrant promoter methylation of FADD and FAS genes were detected in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively, with a significant difference between cases and healthy controls for both FADD and FAS genes (P < 0.001). The gene expression analysis showed statistically significant difference between cases and healthy controls for both FADD (p<0.02) and FAS (p<0.007) genes. CONCLUSIONS: To the best our knowledge, the data of this study are the first report regarding, the effect of promoter hypermethylation of the FADD and FAS genes in development of OSCC. To confirm the data, it is recommended doing further study in large sample sizes in various genetic populations.

Fatal avulsion of choroidal or perforating arteries by guidewires. Case reports, ex vivo experiments, potential mechanisms and prevention.

Innovations in endovascular tools have permitted an increasingly broad range of neurovascular lesions to be treated via minimally invasive methods. However, some device modifications may carry additional risks, not immediately apparent to operators. A patient with a symptomatic, partially thrombosed basilar apex aneurysm was allocated balloon-assisted coiling. Attempts were made to place a microwire across the basilar apex through the posterior communicating artery. Overlapping courses of the posterior cerebral and posterior choroidal arteries on the roadmap images were not recognized and a flanged-tip microwire was inadvertently advanced deep into the choroidal artery. Following the wire with a microcatheter led to binding of arterial tissue within the microcatheter. Removing the wire led to an avulsion of the choroidal artery and a severe hemorrhagic complication which proved fatal. Tissue was identified on the tip of the guidewire. Pathology showed layers of vascular tissue within the laser-cut flanges of the distal wire tip. A similar complication, also fatal, occurred during balloon angioplasty of a distal vertebral artery, when an exchange wire was accidently introduced into a perforator from a posterior cerebral artery. Ex vivo catheterization of distal mesenteric arterial branches showed that the wall of small arteries can be entrapped by laser-cut, flanged, but not by smooth guidewire tips. Microwires with a flanged instead of smooth distal tip, when placed into small caliber vessels, may cause hemorrhagic complications from avulsions*.

Uncertainty and agreement in the management of unruptured intracranial aneurysms.

OBJECT: The management of unruptured intracranial aneurysms remains controversial. The goal of this study was to evaluate the clinical community agreement in decision making regarding unruptured intracranial aneurysms. METHODS: A portfolio of 41 cases of unruptured intracranial aneurysms with angiographic images, along with a short description of the patient presentation, was sent to 28 clinicians (16 radiologists and 12 surgeons) with varying years of experience in the management of unruptured intracranial aneurysms. Five senior clinicians responded twice at least 3 months apart. Nineteen cases (46%) were selected from patients recruited in the Canadian UnRuptured Endovascular versus Surgery trial, an ongoing randomized comparison of coil embolization and clip placement. For each case, the responder was to first choose between 3 treatment options (observation, surgical clip placement, or endovascular coil embolization) and then indicate their level of certainty on a quantitative 0-10 scale. Agreement in decision making was studied using κ statistics. RESULTS: Decisions to coil were more frequent (n = 612, 53%) than decisions to clip (n = 289, 25%) or to observe (n = 259, 22%). Interjudge agreement was only fair (κ = 0.31 ± 0.02) for all cases and all judges, despite substantial intrajudge agreement (range 0.44-0.83 ± 0.10), with high mean individual certainty levels for each case (range 6.5-9.4 ± 2.0 on a scale of 0-10). Agreement was no better within specialties (surgeons or radiologists), within capability groups (those able to perform endovascular coiling alone, surgical clipping alone, or both), or with more experience. There was no correlation between certainty levels and years of experience. Agreement was lower when the cases were taken from the randomized trial (κ = 0.19 ± 0.2) compared with nontrial cases (κ = 0.35 ± 0.2). CONCLUSIONS: Individuals do not agree regarding the management of unruptured intracranial aneurysms, even when they share a background in the same specialty, similar capabilities in aneurysm management, or years of practice. If community equipoise is a necessary precondition for trial participation, this study has found sufficient uncertainty and disagreement among clinicians to justify randomized trials.

Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats.

Administration of the psychostimulant drug amphetamine (AMPH) to animals causes hyperactivity and deficit in prepulse inhibition (PPI) of startle, behaviors that are often observed in neuropsychiatric disorders such as schizophrenia and bipolar disorder. Enhanced central dopamine (DA) transmission is believed to mediate AMPH-induced behavioral alterations. Lithium, a drug used primarily in the treatment of bipolar disorder, is reported to interact with the DA system and antagonize some DA-related behaviors. Here, we provide evidence that AMPH and lithium reciprocally regulate the activity of the transcription factor forkhead box, class O1 (FoxO1), a downstream target of Akt. Administration of d-AMPH (3 mg/kg, intraperitoneally) to Sprague-Dawley rats resulted in a concomitant decrease in levels of phosphorylated (p) Akt as well as p-FoxO1 in the striatum, whereas lithium chloride (LiCl,100 mg/kg, intraperitoneally) exerted the opposite effect, that is, it increased levels of p-Akt and p-FoxO1. Pretreatment of animals with lithium prevented an AMPH-induced decrease in striatal p-Akt and p-FoxO1 levels. Pretreatment of animals with lithium also attenuated AMPH-induced locomotor activity and decreased prepulse inhibition. These in-vivo data suggest that the Akt-FoxO1 pathway may be a common target for the action of dopaminergic and antidopaminergic drugs, and its modulation may be relevant to the treatment of neuropsychiatric disorders.

Intravesical injections of botulinum toxin type A for management of neuropathic bladder: a comparison of two methods.

OBJECTIVES: To evaluate and compare the efficacy of botulinum toxin intravesical injections with and without injections in external urethral sphincter in treating bladder hyper-reflexia in children suffering from myelomeningocele. METHODS: A total of 60 patients with bladder hyper-reflexia due to myelomeningocele were randomly allocated to treatment groups A and B and were followed up for 6 months. Under cystoscopic guidance, 10 IU/kg of botulinum toxin A was injected into the detrusor muscle, sparing the trigone and ureteral orifices in group A. Group B received 8 IU/kg of toxin via the same method compared with group A and 2 IU/kg of toxin through 4 injections in external urethral sphincter. Conventional urodynamics, daily incontinence score, constipation, and creatinine level were evaluated at baseline, 3 months, and 6 months after intervention. Vesicoureteral reflux was also assessed before and after 3 months of injections. RESULTS: All patients showed significant improvement in bladder capacity (P <.01), maximal detrusor pressure (P <.01), and detrusor-sphincter dyssynergia (P <.01) after 3 and 6 months of receiving injections. Significant improvement in postvoiding residual volume was observed only among patients of group B (P <.05). Both methods resulted in a significant reduction in daily incontinence grade, constipation, and vesicoureteral reflux (P <.05), but comparison between the study groups showed better outcomes for group B in relation to incontinency, constipation, vesicoureteral reflux, and creatinine level. CONCLUSIONS: Botulinum toxin type A injections in both sphincter and detrusor seems to have extra benefits such as decreasing postvoiding residual volume and more symptom diminution compared with intradetrusal injections alone.