soning by Nerium oleander as in the case of epileptic patients. BACKGROUND AND AIMS Endoluminal functional luminal imaging probe (EndoFLIP) is an imaging tool that measures physiological characteristics of gastrointestinal sphincters. In this study we used EndoFLIP to evaluate the association between the pyloric physiological measurements with clinical outcomes of gastric peroral endoscopic myotomy (G-POEM) in patients with refractory gastroparesis. METHODS Thirty-seven patients who underwent G-POEM for management of refractory gastroparesis and had EndoFLIP measurements from five centers were evaluated. Cross-sectional area (CSA), balloon pressure (BP), and distensibility index (DI) of the pylorus were evaluated by EndoFLIP at 40 mL and 50 mL balloon fills before and after G-POEM. One-year clinical success and change in gastric emptying study (GES) 3 months after the G-POEM procedure were compared with EndoFLIP measurements. RESULTS Clinical success was achieved in 26 (70%) patients. Post-G-POEM CSA and DI were significantly higher in the clinical success group with both 40 mL (CSA 89.9 ± 64.8 vs 172.5 ± 71.9 mm2, p=0.003; DI 5.8 ± 4.4 vs 8.8 ± 6.1 mm2/mm Hg, p=0.043) and 50 mL volume distention (CSA 140.1 ± 89.9 vs 237.5 ± 80.3 mm2, p=0.003; DI 5.6 ± 3.3 vs 9.9 ± 6.6 mm2/mm Hg, p=0.049). CSA using 40 mL volume distention, with an area under the curve (AUC) of 0.83 yielded specificity of 91% and sensitivity of 71% at a cut-off point of 154 mm2. CONCLUSIONS Post-G-POEM CSA of the pylorus associates with clinical success and improvement of GES after G-POEM. EndoFLIP measurements of pylorus have the potential to be used as a predicting tool of the G-POEM clinical outcome. This review highlights fifty years of progress in research on estradiol’s role in regulating behavior(s). It was initially thought that estradiol was only involved in regulating estrus/menstrual cycles and concomitant sexual behavior, but it is now clear that estradiol also influences the higher order neural function of cognition. We provide a brief overview of estradiol’s regulation of memory and some mechanisms which underlie its effects. Given systemically or directly into the hippocampus, to ovariectomized female rodents, estradiol or specific agonists, enhance learning and/or memory in a variety of rodent cognitive tasks. Acute (within minutes) or chronic (days) treatments enhance cognitive functions. Under the same treatment conditions, dendritic spine density on pyramidal neurons in the CA1 area of the hippocampus and medial prefrontal cortex increase which suggests that these changes are an important component of estrogen’s ability to impact memory processes. Noradrenergic, dopaminergic and serotoninergic activity are also altered in these areas following estrogen treatments. Memory enhancements and increased spine density by estrogens are not limited to females but are also present in castrate males. In the next fifty years, neuroscientists need to determine how currently described neural changes mediate improved memory, how interactions among areas important for memory promote memory and the potential significance of neurally derived estrogens in normal cognitive processing. Answering these questions may provide significant advances for treatment of dementias as well as age and neuro-degenerative disease related memory loss. It is a textbook definition that in the absence of oxygen or inhibition of the mitochondrial respiratory chain by pharmacologic or genetic means, hyper-reduction of the matrix pyridine nucleotide pool ensues due to impairment of complex I oxidizing NADH, leading to reductive stress. However, even under these conditions, the ketoglutarate dehydrogenase complex (KGDHC) is known to provide succinyl-CoA to succinyl-CoA ligase, thus supporting mitochondrial substrate-level phosphorylation (mSLP). Mindful that KGDHC is dependent on provision of NAD+, hereby sources of acute NADH oxidation are reviewed, namely i) mitochondrial diaphorases, ii) reversal of mitochondrial malate dehydrogenase, iii) reversal of the mitochondrial isocitrate dehydrogenase as it occurs under acidic conditions, iv) residual complex I activity and v) reverse operation of the malate-aspartate shuttle. The concept of NAD+ import through the inner mitochondrial membrane as well as artificial means of manipulating matrix NAD+/NADH are also discussed. Understanding the above mechanisms providing NAD+ to KGDHC thus supporting mSLP may assist in dampening mitochondrial dysfunction underlying neurological disorders encompassing impairment of the electron transport chain. BACKGROUND Medial forebrain bundle (MFB) deep brain stimulation (DBS) has anti-depressant effects clinically and in depression models. Currently, therapeutic mechanisms of MFB DBS or how stimulation parameters acutely impact neurotransmitter release, particularly dopamine, are unknown. Experimentally, MFB DBS has been shown to evoke dopamine response in healthy controls, but not yet in a rodent model of depression. OBJECTIVE The study investigated the impact of clinically used stimulation parameters on the dopamine induced response in a validated rodent depression model and in healthy controls. METHOD The stimulation-induced dopamine response in Flinders Sensitive Line (FSL, n = 6) rat model of depression was compared with Sprague Dawley (SD, n = 6) rats following MFB DSB, using Fast Scan Cyclic Voltammetry to assess the induced response in the nucleus accumbens. Stimulation parameters were 130 Hz (“clinically” relevant) with pulse widths between 100 and 350 μs. RESULTS Linear mixed model analysis showed significant impact in both models following MFB DBS both at 130 and 60 Hz with 100 μs pulse width in inducing dopamine response. Furthermore, at 130 Hz the evoked dopamine responses were different across the groups at the different pulse widths. CONCLUSION The differential impact of MFB DBS on the induced dopamine response, including different response patterns at given pulse widths, is suggestive of physiological and anatomical divergence in the MFB in the pathological and healthy state. Selleckchem PMX-53 Studying how varying stimulation parameters affect the physiological outcome will promote a better understanding of the biological substrate of the disease and the possible anti-depressant mechanisms at play in clinical MFB DBS.