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l-Cystine Diamides as l-Cystine Crystallization Inhibitors for Cystinuria

Hu, Longqin; Yang, Yanhui; Aloysius, Herve; Albanyan, Haifa; Yang, Min; Liang, Jian-Jie; Yu, Anthony; Shtukenberg, Alexander; Poloni, Laura N; Kholodovych, Vladyslav; Tischfield, Jay A; Goldfarb, David S; Ward, Michael D; Sahota, Amrik
l-Cystine bismorpholide (1a) and l-cystine bis(N'-methylpiperazide) (1b) were seven and twenty-four times more effective than l-cystine dimethyl ester (CDME) in increasing the metastable supersaturation range of l-cystine, respectively, effectively inhibiting l-cystine crystallization. This behavior can be attributed to inhibition of crystal growth at microscopic length scale, as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective in vivo in a knockout mouse model of cystinuria.
PMCID:5774851
PMID: 27409142
ISSN: 1520-4804
CID: 2211532

Dietary habit and risk of urolithiasis [Meeting Abstract]

Goldfarb, D S
This symposium will review recent information regarding the relationship between diet and kidney stones. Information about diet and its effects on stone risk can be derived from 24 h urine collections. Recommendations regarding diet and beverage use will be surveyed. Proposals regarding randomized controlled trials, both past and future, will be presented
EMBASE:72343739
ISSN: 2194-7228
CID: 2204692

Effect of oxalobacter formigenes colonization on urinary oxalate excretion [Meeting Abstract]

Nazzal, L; Henderson, N; Bedi, S; Francois, F; Perez-Perez, G; Asplin, J R; Goldfarb, D S; Blaser, M J
Kidney stones are a disease of worldwide prevalence with significant public health implications. About 60-80 % of stones are composed of calcium oxalate (CaOx). Hyperoxaluria is a major risk factor. Oxalobacter formigenes (OF), a member of the human colonic microbiota, plays a major role in net colonic oxalate absorption and secretion. We now report OF colonization rates in a young healthy population, the stability of colonization, the effects of antibiotic treatment, and OF colonization on urinary oxalate (Uox) excretion. We followed 64 healthy subjects tested for Helicobacter pylori (HP), who were treated with antibiotics (amoxicillin and clarithromycin for 2 weeks) for HP eradication. Using species-specific PCR, we tested for OF colonization at baseline and at follow-up. Urine samples 3 h after a low oxalate standard meal were analyzed for Uox, factored for urine creatinine (Cr). Of the 65 subjects (M/F: 23/42; mean age 25.2 +/- 5.7 years) tested for OF, 28 (43 %) were positive at baseline. Of 7 OF + subjects at baseline, subject to HP elimination, 6 became OF-negative at 12 wks, only 2 reverted to positive at week 24, and 4 patients remained negative at follow up (Mean 22.5 +/- 4.2 weeks). Of 18 untreated positive people with follow assessments, 16 (89 %) remained positive at follow up (Mean 23.0 +/- 4.2 week), but of 24 untreated negative subjects, only 3 (12 %) were positive at follow up (mean 20.2 +/- 6.8 weeks), significantly fewer than the untreated positives (p = 0.001 by Fisher exact test). We tested Uox/Cr in 137 samples from 46 subjects with no antibiotic exposure at different time points. We found that the presence of OF was associated with 14 % lower Uox/cr as compared with its absence (17.0 +/- 0.0 vs 19.4 +/- 0.1 mg/g, p = 0.04). We conclude that OF colonization status remains stable over a follow- up period of several months, with antibiotics suppressing colonization in the majority of people in the short term. The differences in urinary oxalate levels with respect to OF status is consistent with its protective effects for the prevention of calcium oxalate kidney stones
EMBASE:72343901
ISSN: 2194-7228
CID: 2204652

Prospects for dietary therapy of urolithiasis [Meeting Abstract]

Goldfarb, D S
Diet, of course, influences urine chemistry. Yet only one randomized controlled trial has demonstrated that a change in diet led to reduction in stone recurrence. I will review some of the deficiencies in the current scientific dietary literature and suggest how these deficiencies could be addressed. Highlights will include comparisons of diet with pharmacologic therapy, how prescribing dietary patterns, rather than individual nutrients, might be a preferable way to address therapy, and the possible effect of the microbiome on how diet influences urinary chemistry
EMBASE:72343742
ISSN: 2194-7228
CID: 2204682

An analysis of the effect of 3D printed renal cancer models on surgical planning [Meeting Abstract]

Rude, T; Wake, N; Sodickson, D K; Stifelman, M; Borin, J; Chandarana, H; Huang, W C
Purpose Pre-operative three-dimensional (3D) printed renal malignancy models are tools with potential benefits in surgical training and patient education [1,2]. Most importantly, 3D models may facilitate surgical planning by allowing surgeons to assess tumor complexity as well as the relationship of the tumor to major anatomic structures [3]. The objective of this study was to evaluate this impact. Methods Imaging was obtained from an IRB approved, prospectively collected database of multiparametric magnetic resonance imaging (MRI) of renal masses. Ten cases eligible for elective partial nephrectomy were retrospectively selected. High-fidelity models were 3D printed in multiple colors based on T1 images (Fig. 1). Cases were reviewed by three attending surgeons and six senior residents with imaging alone and in addition to the 3D model. A standardized questionnaire was developed to capture the planned surgical approach and intraoperative technique in both sessions. Results Surgical approach was changed in 20 % of decisions, intraoperative considerations were changed in 40 % (Fig. 2). Thirty percent and 23 % of decisions in the attending and resident groups, respectively, were altered by the 3D model. Overall, every case was modified with this additional information. All participants reported that the models helped plan the surgical approach for partial nephrectomy. Most reported improved comprehension of anatomy and confidence in surgical plan. Half reported that the 3D printed model altered their surgical plan significantly. Due to use of T1 images, reconstruction of calyces and tertiary blood vessels were limited: 8 of the 9 participants desired more information regarding these structures. (Figure presented) Conclusion Utilization of 3D modeling may aid in pre-operative and intra-operative planning for both attending and resident surgeons. While 3D models with MR imaging is feasible, computed tomography (CT) imaging may provide additional anatomical information. Future study is required to prospectively assess the utility of models and pre-operative planning and intra-operative guidance
EMBASE:72343154
ISSN: 1861-6410
CID: 2204702

Heat equation inversion framework for average SAR calculation from magnetic resonance thermal imaging

Alon, Leeor; Sodickson, Daniel K; Deniz, Cem M
Deposition of radiofrequency (RF) energy can be quantified via electric field or temperature change measurements. Magnetic resonance imaging has been used as a tool to measure three dimensional small temperature changes associated with RF radiation exposure. When duration of RF exposure is long, conversion from temperature change to specific absorption rate (SAR) is nontrivial due to prominent heat-diffusion and conduction effects. In this work, we demonstrated a method for calculation of SAR via an inversion of the heat equation including heat-diffusion and conduction effects. This method utilizes high-resolution three dimensional magnetic resonance temperature images and measured thermal properties of the phantom to achieve accurate calculation of SAR. Accuracy of the proposed method was analyzed with respect to operating frequency of a dipole antenna and parameters used in heat equation inversion. Bioelectromagnetics. 2016;9999:1-11. (c) 2016 Wiley Periodicals, Inc.
PMCID:5538363
PMID: 27490064
ISSN: 1521-186x
CID: 2199532

Sleep and mealtime misalignment alters functional connectivity: A pilot resting state study

Yoncheva, Y N; Castellanos, F X; Pizinger, T; Kovtun, K; St-Onge, M-P
Delayed sleep and meal times promote metabolic dysregulation and obesity. Altered coordination of sleeping and eating times may impact food reward valuation and interoception in the brain, yet the independent and collective contributions of sleep and meal times are unknown. This randomized, inpatient crossover study experimentally manipulates sleep and meal times while preserving sleep duration (7.05+/-0.44 h for 5 nights). Resting-state functional MRI scans (2 x 5-minute runs) were obtained for 4 participants (3 males; 25.3+/-4.6 y), each completing all study phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; late sleep/late meal). Normal mealtimes were 1, 5, 11, and 12.5 h after awakening; late mealtimes were 4.5, 8.5, 14.5 and 16 h after awakening. Seed-based resting-state functional connectivity (RSFC) was computed for a priori regions-of-interest (seeds) and contrasted across conditions. Statistically significant (P<0.05, whole-brain corrected) regionally-specific effects were found for multiple seeds. The strongest effects were linked to the amygdala: increased RSFC for late versus normal mealtimes (equivalent to skipping breakfast). A main effect of sleep and interaction with mealtime were also observed. Preliminary findings support the feasibility of examining the effects of sleep and meal time misalignment, independent of sleep duration, on RSFC in regions relevant to food reward and interoception.International Journal of Obesity accepted article preview online, 01 August 2016. doi:10.1038/ijo.2016.132.
PMCID:5101157
PMID: 27478925
ISSN: 1476-5497
CID: 2199402

GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits

Tremblay, Robin; Lee, Soohyun; Rudy, Bernardo
Cortical networks are composed of glutamatergic excitatory projection neurons and local GABAergic inhibitory interneurons that gate signal flow and sculpt network dynamics. Although they represent a minority of the total neocortical neuronal population, GABAergic interneurons are highly heterogeneous, forming functional classes based on their morphological, electrophysiological, and molecular features, as well as connectivity and in vivo patterns of activity. Here we review our current understanding of neocortical interneuron diversity and the properties that distinguish cell types. We then discuss how the involvement of multiple cell types, each with a specific set of cellular properties, plays a crucial role in diversifying and increasing the computational power of a relatively small number of simple circuit motifs forming cortical networks. We illustrate how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.
PMCID:4980915
PMID: 27477017
ISSN: 1097-4199
CID: 2198482

Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease

Mauricio, Rina; Srichai, Monvadi B; Axel, Leon; Hochman, Judith S; Reynolds, Harmony R
BACKGROUND: In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). HYPOTHESIS: Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. METHODS: Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average
PMID: 27459149
ISSN: 1932-8737
CID: 2191502

The enigmatic mossy cell of the dentate gyrus

Scharfman, Helen E
Mossy cells comprise a large fraction of the cells in the hippocampal dentate gyrus, suggesting that their function in this region is important. They are vulnerable to ischaemia, traumatic brain injury and seizures, and their loss could contribute to dentate gyrus dysfunction in such conditions. Mossy cell function has been unclear because these cells innervate both glutamatergic and GABAergic neurons within the dentate gyrus, contributing to a complex circuitry. It has also been difficult to directly and selectively manipulate mossy cells to study their function. In light of the new data generated using methods to preferentially eliminate or activate mossy cells in mice, it is timely to ask whether mossy cells have become any less enigmatic than they were in the past.
PMCID:5369357
PMID: 27466143
ISSN: 1471-0048
CID: 2191602