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Throughout the developing nervous system, neural stem and progenitor cells give rise to diverse classes of neurons and glia in a spatially and temporally coordinated manner. In the ventral spinal cord, much of this diversity emerges through the morphogen actions of Sonic hedgehog (Shh). Interpretation of the Shh gradient depends on both the amount of ligand and duration of exposure, but the mechanisms permitting prolonged responses to Shh are not well understood. We demonstrate that Notch signaling plays an essential role in this process, enabling neural progenitors to attain sufficiently high levels of Shh pathway activity needed to direct the ventral-most cell fates. Notch activity regulates subcellular localization of the Shh receptor Patched1, gating the translocation of the key effector Smoothened to primary cilia and its downstream signaling activities. These data reveal an unexpected role for Notch shaping the interpretation of the Shh morphogen gradient and influencing cell fate determination.

Introduction: Fluoxetine is a prototype drug of the Selective Serotonin Reuptake Inhibitors (SSRIs) group of antidepressants. SSRIs help prostatic disease patients by improving quality of life in terms of decreased requirement of anti-inflammatory and antibiotic medication, decreasing the pain in the genital area, pain, and difficulty during urination, and improving urinary flow. Aim: To investigate histological changes in the prostate (dorsolateral lobe) produced by different doses (10, 20 and 40 mg/kg/day) of fluoxetine given for different duration (Phases) in adult male albino rats. Materials and Methods: An experimental study was done in the Anatomy Department, Himalayan Institute Medical Sciences (HIMS), Swami Rama Himalayan University, Jolly Grant, Dehradun, Uttarakhand, INDIA. The duration of the study was twelve months from May 2009-April 2010. Present study was done on 36 adult male albino rats divided into Control (Group 1) and Experimental (Group 2, 3 and 4). Rats received 10 mg/kg/day, 20 mg/kg/day, and 40 mg/kg/day of fluoxetine intraperitoneally (I/P) for phases of 2 weeks, 4 weeks, and 12 weeks. Prostate (dorsolateral lobe) tissue was collected, processed, and examined in a light microscope after Haematoxylin and Eosin (H&E) staining. Morphometric and statistical analysis (mean, standard deviation and student's t-test) was done. Results: Group 2 rats received fluoxetine for 12 weeks, Group 3 rats received fluoxetine for 4 weeks and 12 weeks, and Group 4 rats received fluoxetine for 7-10 days showed histological changes in the dorsolateral lobe of the prostate gland and stroma in the form of Smooth Muscle (SM) hypertrophy, epithelial cell changes (become cuboidal to flatten), epithelial cell degeneration, decreased diameter of the prostate acinus, and decrease in epithelial infoldings. Conclusion: Fluoxetine (SSRI) alters the histology (both glandular acini as well as stroma) of the dorsolateral lobe of the prostate if used in low doses for a long duration, moderate doses for a few weeks and also for a long duration, and high dose for one week. This changed histology might be helpful in relieving the symptoms, pain, and discomfort felt by prostatic disease patients. [ABSTRACT FROM AUTHOR]

Most current PET detector designs suffer from event mispositioning at high count rates, as scintillation light from nearby and nearly simultaneous gamma ray conversions becomes mixed. We have used the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source to quantify this effect as a function of activity on two block-detector tomographs (the Siemens/CTI HR+ and the General Electric Discovery LS), and two Anger-type PET tomographs (the Siemens ECAM DUET and the Philips CPET+). After accounting for event losses due to dead time, we find that the number of counts on LORs passing through a cylinder of diameter and height equal to the point-source full width at tenth-maximum measured at low rate surrounding the point source decreases by between 9% (HR+) and 35% (CPET+) at the activity giving rise to peak noise equivalent count (NEC) rate. Mispositioned events act to reduce signal-to-noise ratio, both by reducing apparent activity at the originating location and by increasing the signal background. We have reformulated the conventional expression for NEC rate to account for this phenomenon. The new formulation of NEC, which we call NEC*, results in a lower peak value which in turn occurs at a lower activity concentration than for the conventional formulation. Index Terms--Count-rate, data quality, NEC, PET, pileup.

Introduction: Fluoxetine and other Selective Serotonin Reuptake Inhibitors (SSRIs) are reported to produce hyponatremia especially in elderly patients. Aim: To evaluate histological changes in kidney tissue of albino rats by different doses of fluoxetine for different duration and changes in the mean diameter of Proximal Convoluted Tubules (PCT) and Distal Convoluted Tubules (DCT) in control and experimental group was observed. Materials and Methods: An Experimental study was conducted in which total of 72 albino rats (36 male and 36 female) received single different doses-Mild (10 mg/Kg/day), moderate (20 mg/kg/day) and high (40 mg/kg/day) of intraperitoneal injection of fluoxetine hydrochloride daily for 14 days (2 weeks), 28 days (4 weeks) and 84 days (12 weeks). Changes in kidney tissue histology were investigated and changes in the mean diameter of PCT and Distal convoluted tubules were also observed. Results: Mild and moderate doses of fluoxetine hydrochloride produce changes in the kidney histology in the form of appearance of podocytes bridge, degenerated/shrunken and swollen glomerulus, dilated tubules when given for long duration. High doses of fluoxetine change kidney histology within few days in the form of hypercellular shrunken glomerulus with apparently increased urinary/capsular space, appearance of podocytes bridge, dilated and degenerated tubules with presence of cast. Mean diameter of PCT was found to be increased in experimental rats in comparison to control rats (p<0.01) but there was no statistical significant change in diameter of DCT. Conclusion: The findings showed that fluoxetine produce changes in kidney histology both at the level of glomerulus and tubules. [ABSTRACT FROM AUTHOR]

Introduction: Selective Serotonin Re-uptake Inhibitors (SSRIs) are the most significant and safe drugs among the antidepressants. Fluoxetine is the prototype drug of SSRIs. Various clinical studies showed that SSRI causes change in body weight in patients. This study was conducted to know the extent of weight change with different doses for different durations. Aim: The aim of this study was to find out whether fluoxetine causes weight gain or weight loss, and to deduce the comparative weight change after intraperitoneal injection of fluoxetine for different duration and doses. Materials and Methods: Present study was conducted on 72 adult (36 males and 36 females) albino rats, in 3 phases of 2 weeks, 4 weeks and 12 weeks duration. Each phase consisted of 24 (12 males and 12 females) albino rats. These 24 rats were further randomly subdivided into 4 Groups of 6 albino rats each (3 males & 3 females). Group 1(Control) received normal saline (vehicle). Rest 18 rats of each phase were experimental rats, of Group 2, Group 3 and Group 4 (6 rats each). Group 2, group 3 and group 4 experimental rats received 10mg/kg, 20 mg/kg and 40mg/kg of intraperitoneal injection of fluoxetine respectively. All rats were weighed on each day for growth monitoring. Data was subjected to statistical analysis (Mean, standard deviation and Student's t-Test). Results: All experimental group rats which received fluoxetine showed decrease of body weight. Rats which received high doses of fluoxetine could not tolerate the drug for more than two weeks and died due to excessive body weight loss, loose stools and muscle twitching. Conclusion: Present study conclude that SSRIs can cause weight change in the form of decrease of body weight. This property of SSRIs can be used clinically by prescribing these drugs to obese psychiatric patient without any fear of withdrawal of drug. [ABSTRACT FROM AUTHOR]

BACKGROUND: Because serum creatinine is an insensitive measure of kidney dysfunction, guidelines have advocated routine use of estimated glomerular filtration rate (eGFR) to identify patients with chronic kidney disease (CKD). Patients with early (stage 3) CKD remain undiagnosed in primary care clinics; therefore, we hypothesized that routine reporting of eGFR in outpatient clinics would improve the recognition and treatment of CKD. METHODS: A retrospective review of primary care patients was undertaken at the Bronx Veterans Affairs Medical Center, Bronx, New York, before and after the institution of routine eGFR reporting. We evaluated the achievement of diagnostic and therapeutic treatment goals based on the Kidney Disease Outcomes Quality Initiative guidelines (documentation of CKD, urinalysis assessment, blood pressure < 130/80 mm Hg, and renin-angiotensin system blockade) for patients with stage 3 CKD during each period. RESULTS: Overall, patients with diabetes with early-stage CKD achieved superior treatment rates than similar patients without diabetes. Routine reporting of eGFR improved the documentation and identification of CKD by almost 50%, although absolute improvement was modest. Use of renin-angiotensin system blockers improved minimally, as did blood pressure control. Patients with documented CKD achieved treatment goals more frequently than patients without documented CKD. CONCLUSION: Routine reporting of eGFR alone modestly improved the identification of patients with CKD without a clinically significant effect on care. For Modification of Diet in Renal Disease Study calculation of eGFR reporting to effect improvements in CKD care, it will be necessary to pair eGFR reporting with provider education to identify these patients and treat them effectively.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Increases in average density have been observed during lower-hybrid current-drive experiments (LHCD) on the Versator II tokamak [Phys. Rev. Lett. 48, 152 (1982)], and on other LHCD experiments where inductive-Ohmic and lower-hybrid current drive are combined. In the present experiment it is found that this density increase is the result of an improvement in global particle confinement time τ[sub p] in comparison to purely Ohmic discharges with similar plasma parameters. Furthermore, it is found that the improved confinement deteriorates when the anomalous Doppler relaxation instability of the anisotropic high-energy electron tail becomes unstable during LHCD, and the loss rate of tail electrons increases. However, energetic electron losses alone are at least an order of magnitude too small to explain this deterioration in particle confinement. [ABSTRACT FROM AUTHOR]