What ' s known on the subject? and What does the study add? During radical prostatectomy, urological surgeons have tried to identify the " cord-like NVB " at the lateral aspect of the prostate. However, little histological or physiological investigation was conducted to verify that the NVB identifi ed at surgery really included the cavernous nerve. Recently, there have been observations that refute the dogma that the cavernous nerve is always within the NVB.In this study, we have described a hammock-like distribution of the nerves on which the prostate rests, demonstrating that the NVB is more a network of multiple fi ne dispersed nerves than a distinct structure. We presented a novel nerve-sparing approach to complete hammock preservation. This risk-stratifi ed approach for determining the degree of nerve sparing based on the patient ' s likelihood of ipsilateral EPE seeks to categorize patients for optimal balance between oncological outcomes and functional outcomes. OBJECTIVES• To report the potency and oncological outcomes of patients undergoing robotassisted radical prostatectomy (RARP) using a risk-stratifi ed approach based on layers of periprostatic fascial dissection.• We also describe the surgical technique of complete hammock preservation or nerve sparing grade 1. PATIENTS AND METHODS• This is a retrospective study of 2317 patients who had robotic prostatectomy by a single surgeon at a single institution between January 2005 and June 2010.• Included patients were those with ≥ 1 year of follow-up and who were potent preoperatively, defi ned as having a sexual health inventory for men (SHIM) questionnaire score of > 21; thus, the fi nal number of patients in the study cohort was 1263.• Patients were categorized pre-operatively by a risk-stratifi ed approach into risk grades 1 -4, where risk grade 1 patients received nerve-sparing grade 1 or complete hammock preservation and so on for risk grades 2 -4, as long as intraoperative fi ndings permitted the planned nerve sparing.• We considered return to sexual function post-operatively by two criteria: i) ability to have successful intercourse (score of ≥ 4 on question 2 of the SHIM) and ii) SHIM > 21 or return to baseline sexual function. RESULTS• There was a signifi cant difference across different NS grades in terms of the percentages of patients who had intercourse and returned to baseline sexual function ( P < 0.001), with those that underwent NS grade 1 having the highest rates (90.9% and 81.7%) as compared to NS grades 2 (81.4% and74.3%), 3 (73.5% and 66.1%), and 4 (62% and 54.5%).• The overall positive surgical margin (PSM) rates for patients with NS grades 1, 2, 3, and 4 were 9.9%, 8.1%, 7.2%, and 8.7%, respectively ( P = 0.636).• The extraprostatic extension rates were 11.6%, 14.3%, 29.3%, and 36.2%, respectively ( P < 0.001).• Similarly, in patients younger than 60, intercourse and return to baseline sexual function rates were 94.9% and 84.3% for NS grade 1 as compared to 85.5% and 77.2% for NS grades 2, 76.9% and 69% for NS grades 3, and 64.8% and...

Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75) consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9) for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d, with d indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (MTHFR) rs1801133, methionine synthase (MTR) rs1805087 [wild-type (WT)], MTR reductase (MTRR) rs1801394, and methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis via the cytidine diphosphate (CDP)-choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg/d restored partitioning of dietary choline between betaine and CDP-PC among NP (MTHFR rs1801133 and MTR rs1805087 WT) and lactating (MTHFD1 rs2236225) women with risk genotypes. Overall, our findings indicate that loss-of-function variants in folate-metabolizing enzymes strain cellular PC production, possibly via impaired folate-dependent phosphatidylethanolamine-N-methyltransferase (PEMT)-PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.-Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J. C., Ganti, A., Carrier, B., Yan, J., Taeswuan, S., Cohen, V. V., Swersky, C. C., Stover, J. A., Vitiello, G. A., Malysheva, O. V., Mudrak, E., Caudill, M. A. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

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