Glycal Metallanitrenes for 2-Amino Sugar Synthesis: Amidoglycosylation of Gulal-, Allal-, Glucal-, and Galactal 3-Carbamates.

The rhodium(II)-catalyzed oxidative cyclization of glycal 3-carbamates with in situ incorporation of an alcohol nucleophile at the anomeric position provides access to a range of 2-amino sugars having 1,2-trans-2,3-cis stereochemistry, a structural motif present in compounds of medicinal and biological significance such as the streptothricin group of antibiotics and the Chitinase inhibitor allosamidin. All of the diastereomeric d-glycal 3-carbamates have been investigated, revealing significant differences in anomeric stereoselectivity depending on substrate stereochemistry and protecting groups. In addition, some substrates were prone to forming C3-oxidized dihydropyranone byproducts under the reaction conditions. Allal- and gulal 3-carbamates provided uniformly high stereo- and chemoselectivity, while for glucal substrates, acyclic, electron-withdrawing protecting groups at the 4 O and 6 O positions were required. Galactal 3-carbamates have been the most challenging substrates; formation of their amidoglycosylation products is most effective with an electron-withdrawing 6 O-Ts substituent and a sterically demanding 4 O-TBS group. These results suggest a mechanism whereby conformational and electronic factors determine the partitioning of an intermediate acyl nitrenoid between alkene addition, leading to amidoglycosylation, and C3-H insertion, providing the dihydropyranone byproduct. Along the amidoglycosylation pathway, high anomeric selectivity results when a glycosyl aziridine intermediate is favored over an aziridine-opened oxocarbenium donor.

Magnetic Resonance Imaging-Directed Ultrasound Imaging of Non-Mass Enhancement in the Breast: Outcomes and Frequency of Malignancy.

OBJECTIVES: This study was performed to determine the frequency, predictors, and outcomes of ultrasound (US) correlates for non-mass enhancement. METHODS: From January 2005 to December 2011, a retrospective review of 5837 consecutive breast magnetic resonance imaging examinations at our institution identified 918 non-mass enhancing lesions for which follow-up or biopsy was recommended. Retrospective review of the images identified 879 of 918 lesions (96%) meeting criteria for non-mass enhancement. Patient demographics, pathologic results, and the presence of an adjacent landmark were recorded. Targeted US examinations were recommended for 331 of 879 cases (38%), and 284 of 331 women (86%) underwent US evaluations. RESULTS: The US correlate rate for non-mass enhancement was 23% (64 of 284). An adjacent landmark was significantly associated with a US correlate (P < .001). Biopsy was recommended for 43 of 64 correlates (67%). Ultrasound-guided biopsy was performed on 39 of 43 (91%); 7 of 39 (18%) were malignant. No correlate was seen for 220 of 284 lesions (77%). At magnetic resonance imaging-guided biopsy, 14 of 117 (12%) were malignancies. For all biopsied non-mass enhancements, the malignancy rate was 18% (55 of 308) and was significantly more prevalent in the setting of a known index cancer (P < .001), older age (P < .001), the presence of a landmark (P = .002), and larger lesion size (P = .019). CONCLUSIONS: Non-mass enhancement with an adjacent landmark is more likely to have a US correlate compared to non-mass enhancement without an adjacent landmark. Non-mass enhancement in the setting of a known index cancer, older age, a landmark, and larger lesion size is more likely to be malignant. However, no statistical difference was detected in the rate of malignancy between non-mass enhancement with (18%) or without (12%) a correlate. Absence of a correlate does not obviate the need to biopsy suspicious non-mass enhancement.

Oily fish consumption is inversely correlated with cerebral microbleeds in community-dwelling older adults: results from the Atahualpa Project.

BACKGROUND: Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). These nutrients improve endothelial dysfunction, reduce ß-amyloid induced damage of neurovascular units, and might prevent the occurrence of cerebral microbleeds. However, this relationship has not been investigated so far. AIM: To evaluate the association between oily fish intake and cerebral microbleeds in a population of frequent fish consumers living in coastal Ecuador. METHODS: Cerebral microbleeds were identified by gradient-echo MRI and oily fish consumption was calculated in community-dwellers aged ≥60 years enrolled in the Atahualpa Project. The association between cerebral microbleeds and fish servings was examined in regression models adjusted for relevant confounders. A predictive model was constructed using quintiles of fish servings to take into account the non-linearity in the relationship. RESULTS: Out of 311 eligible individuals, 293 (94 %) were enrolled. Cerebral microbleeds were recognized in 37 (13 %) individuals. Mean fish consumption was 8.8 ± 5.4 servings per week (ω-3 PUFAs estimates: 10.2 ± 7.1 g). Multivariate analysis showed an inverse relationship between cerebral microbleeds and fish consumption (p < 0.001). Predictive margins of CMB were higher for individuals in the lowest (≤4.3) than for those in the highest (≥13.1) quintile of fish servings (17.4 vs 2.3 %, p < 0.001). CONCLUSIONS: This study shows a lower cerebral microbleed presence among older adults eating large amounts of oily fish (13 servings per week, equivalent to about 15 g of ω-3 PUFAs). These high requirements can be more readily accomplished in other populations by taking fish oil preparations. Longitudinal studies are warranted to assess whether these interventions reduce incident cerebral microbleeds in high-risk individuals.

Oily Fish Intake and Cognitive Performance in Community-Dwelling Older Adults: The Atahualpa Project.

Due to their high content of omega-3 polyunsaturated fatty acids, oily fish consumption is likely associated with a better cognitive performance. However, information on this association is controversial, with some studies showing a positive effect while others showing no association. We aimed to assess the effects of oily fish consumption on cognitive performance in a population of frequent fish consumers living in rural coastal Ecuador. Atahualpa residents aged ≥60 years were identified during a door-to-door survey and evaluated by the use of the Montreal Cognitive Assessment (MoCA). Oily fish servings per week were calculated in all participants. We estimated whether fish intake correlated with MoCA scores in generalized multivariate linear models adjusted for demographics, cardiovascular risk factors, edentulism and symptoms of depression. Out of 330 eligible persons, 307 (93%) were enrolled. Mean MoCA scores were 19 ± 4.8 points, and mean oily fish consumption was 8.6 ± 5.3 servings per week. In multivariate analyses, MoCA scores were related to fish servings (ß 0.097, 95% CI 0.005-0.188, p = 0.038). Locally weighted scatterplot smoothing showed an inflection point in the total MoCA score curve at four fish servings per week. However, predictive margins of the MoCA score were similar across groups below and above this point, suggesting a direct linear relationship between oily fish intake and cognitive performance. Simple preventive measures, such as modifying dietary habits might be of value to reduce the rate of cognitive decline in community-dwelling older adults living in underserved populations.

68 Ga-DOTATATE PET to Characterize Lesions in the Neuroaxis.

AIM: The differentiation of paragangliomas, schwannomas, meningiomas, and other neuroaxis tumors in the head and neck remains difficult when conventional MRI is inconclusive. This study assesses the utility of 68 Ga-DOTATATE PET/CT as an adjunct to hone the diagnosis. PATIENTS AND METHODS: This retrospective study considered 70 neuroaxis lesions in 52 patients with 68 Ga-DOTATATE PET/CT examinations; 22 lesions (31%) had pathologic confirmation. Lesions were grouped based on pathological diagnosis and best radiologic diagnosis when pathology was not available. Wilcoxon rank sum tests were used to test for differences in SUV max among paragangliomas, schwannomas, and meningiomas. Receiver operator characteristic curves were constructed. RESULTS: Paragangliomas had a significantly greater 68 Ga-DOTATATE uptake (median SUV max , 62; interquartile range [IQR], 89) than nonparagangliomas. Schwannomas had near-zero 68 Ga-DOTATATE uptake (median SUV max , 2; IQR, 1). Intermediate 68 Ga-DOTATATE uptake was seen for meningiomas (median SUV max , 19; IQR, 6) and other neuroaxis lesions (median SUV max , 7; IQR, 9). Receiver operator characteristic analysis demonstrated an area under the curve of 0.87 for paragangliomas versus all other lesions and 0.97 for schwannomas versus all other lesions. CONCLUSIONS: Marked 68 Ga-DOTATATE uptake (>50 SUV max ) favors a diagnosis of paraganglioma, although paragangliomas exhibit a wide variability of uptake. Low to moderate level 68 Ga-DOTATATE uptake is nonspecific and may represent diverse pathophysiology including paraganglioma, meningioma, and other neuroaxis tumors but essentially excludes schwannomas, which exhibited virtually no uptake.

18F-FDG PET/CT for the Evaluation of Therapy Response in Hormone Receptor-Positive Bone-Dominant Metastatic Breast Cancer.

Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has shown promise for use in assessing treatment response in patients with bone-only or bone-dominant (BD) metastatic breast cancer (mBC). In this single-institution, prospective single-arm study of 23 women (median age, 59 years [range, 38-81 years]) with biopsy-proven estrogen receptor-positive bone-only or BD mBC about to begin new endocrine therapy between October 3, 2013, and August 3, 2018, the value of early 4-week 18F-FDG PET/CT in predicting progression-free survival (PFS) was evaluated. 18F-FDG PET/CT was performed at baseline, 4 weeks, and 12 weeks. Maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) were measured for up to five index lesions. The primary end point was PFS. Secondary end points were overall survival (OS) and time to skeletal-related events (tSREs). All end points were compared between responders (reduction of 30% or more in the sum of SUVmax for target lesions) and nonresponders at 4 weeks and 12 weeks. Percentage change from baseline in SUVmax at 4- and 12-week 18F-FDG PET/CT were highly correlated (r = 0.81). At the 4-week time point PET responders had numerically longer PFS (14.2 months vs 6.3 months; P = .53), OS (44.0 months vs 29.7 months; P = .47), and tSRE (27.4 months vs 25.2 months; P = .66) compared with nonresponders, suggesting the clinical utility of 4-week 18F-FDG PET/CT as an early predictor of treatment failure. Keywords: Breast Cancer, Metastatic Breast Cancer, Bone-Dominant Metastatic Breast Cancer, FDG PET/CT, Estrogen-Receptor Positive Metastatic Breast Cancer Supplemental material is available for this article. Clinical trial registration no. NCT04316117 © RSNA, 2022.

Perfusion-only imaging in pregnant women: A comparative reader study with implications for practice patterns.

This study seeks to understand the value of ventilation imaging in pregnant patients imaged for suspected pulmonary embolism (PE). Ventilation-perfusion (VQ) scans in this high-risk population were compared to ventilation-only scans. We hypothesize that in this relatively healthy population, the exclusion of ventilation scans will not impact the rate of scans interpreted as positive. This retrospective blinded comparative reader study on collated VQ scans performed on pregnant patients in the course of routine clinical care in a > 5 year period (03/2012 to 07/2017). Each set of VQ and perfusion only (Q) studies were reviewed by 8 readers (4 nuclear radiology fellows and 4 nuclear medicine faculty) in random order; the Q scans simply omitted the ventilation images. Readers recorded each study as PE, no PE, or non-diagnostic (prospective investigative study of acute PE diagnosis classifications). Logistic mixed effects models were used to test the association between scan type (VQ vs Q). 203 pairs of studies in 197 patients were included (6 patients had 2 scans). Subjects ranged from 14 to 45 years of age, with a median 28 years. A significant association between scan type and positive/negative classification. Q-scans received more positive classifications than VQ-scans (median of 7.6% vs 6.7%). No association was seen between scan type and positive/indeterminate classification, nor between scan type and negative/indeterminate classification. The exclusion of ventilation images in VQ-scans was associated with a higher rate of positive studies, but this difference was small (<1%). Given the overwhelmingly normal percentage of Q-exams (>90% in our study), and the benefits of omitting ventilation imaging, perfusion-only imaging should be considered a reasonable option for imaging the pregnant patient to exclude PE.

18F-Fluciclovine PET/CT in Therapeutic Decision Making for Prostate Cancer: A Large Single-Center Practice-Based Analysis.

METHODS: We carried out a retrospective cohort study of patients with BR after primary treatment of PC who received imaging with 18F-fluciclovine PET/CT at our institution between January 2010 and January 2019. PET/CT results were compared with biopsy, conventional imaging results, and/or response to PC therapy. 18F-Fluciclovine PET/CT performance statistics and effects on treatment planning were calculated. RESULTS: A total of 328 patients with a median age of 71 years (range, 47-90 years) and median serum prostate-specific antigen level of 1.6 ng/mL (0.02-186.7 ng/mL) were included. Three hundred thirty-six 18F-fluciclovine PET/CT scans were analyzed and classified as positive (65%), negative (25%), or equivocal (10%) based on radiology reports. Sensitivity was 93% (95% confidence interval, 86%-96%) and specificity was 63% (95% confidence interval, 45%-77%). Of patients with known management recommendations post-PET/CT, scan results changed or influenced pre-PET/CT management plans in 73%, and 58% of recommendations involved treatment modality decisions. Overall, 82% of patients' actual management was concordant with post-PET/CT recommendations. Of evaluable patients, 116 (35%) had some form of post-PET radiotherapy included in their care plans, with 95% receiving radiotherapy at a PET-avid target. CONCLUSIONS: In the largest single-institutional cohort to date, 18F-fluciclovine PET/CT showed value in the workup of PC in the setting of BR, with noteworthy influence over clinical management decisions. Further studies are needed to evaluate whether PET/CT-based changes in management are associated with improved outcomes.

PET in Pediatric Lymphoma.

Although fluorodeoxyglucose PET/MR imaging is a promising new modality, there is not yet enough data to support its routine use for staging or surveillance of children with lymphoma. PET/MR imaging protocols are still under development, and its availability globally is limited. The cost-benefit of using PET/MR imaging has not yet been established, especially because annual post-treatment surveillance imaging with fluorodeoxyglucose PET is not necessary in most patients with lymphoma. Further research into the use of PET/MR imaging in pediatric oncology patients is needed with continued collaborations among institutions.

Update on Quantitative Imaging for Predicting and Assessing Response in Oncology.

Molecular imaging has revolutionized clinical oncology by imaging-specific facets of cancer biology. Through noninvasive measurements of tumor physiology, targeted radiotracers can serve as biomarkers for disease characterization, prognosis, response assessment, and predicting long-term response/survival. In turn, these imaging biomarkers can be utilized to tailor therapeutic regimens to tumor biology. In this article, we review biomarker applications for response assessment and predicting long-term outcomes. 18F-fluorodeoxyglucose (FDG), a measure of cellular glucose metabolism, is discussed in the context of lymphoma and breast and lung cancer. FDG has gained widespread clinical acceptance and has been integrated into the routine clinical care of several malignancies, most notably lymphoma. The novel radiotracers 16α-18F-fluoro-17ß-estradiol and 18F-fluorothymidine are reviewed in application to the early prediction of response assessment of breast cancer. Through illustrative examples, we explore current and future applications of molecular imaging biomarkers in the advancement of precision medicine.

Dietary Oily Fish Intake and Frailty. A Population-Based Study in Frequent Fish Consumers Living in Rural Coastal Ecuador (the Atahualpa Project).

Oily fish are recommended as part of a healthy diet due to their high content of long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), proteins, and other nutrients. There is preliminary evidence of beneficial effects of ω-3 PUFAs in the prevention of sarcopenia (a major component of frailty). In this study, we aimed to assess the relationship between dietary oily fish intake and a measure of frailty - the Edmonton Frail Scale (EFS) score - in community-dwelling older adults living in rural coastal Ecuador. A total of 363 Atahualpa residents were enrolled. The mean fish servings per week were 8.8 ± 5.2 and mean EFS score was 5 ± 2.8 points. A linear regression model showed no association between the amount of oily fish intake and EFS scores. However, an interaction model, with participants stratified according to their median age and fish intake in quintiles, showed a significant effect for both variables on the EFS score (ß coefficient = 0.104; 95% C.I.: 0.003-0.206; p = 0.044). At the lowest quintile of fish intake, younger individuals have lower EFS scores than their older counterparts. As the consumption of oily fish increases, mean EFS scores margins were found to be progressively reduced in subjects aged 60-69 years but were largely unaffected in persons aged ≥70 years. It appears that oily fish intake has a positive effect on the frailty status of younger subjects but is superseded by the effects of age in the older population.

The relationship of obesity, mammographic breast density, and magnetic resonance imaging in patients with breast cancer.

PURPOSE: The purpose was to evaluate the relationship between body mass index (BMI), mammographic breast density, magnetic resonance (MR) background parenchymal enhancement (BPE), and MR fibroglandular tissue (FGT) in women with breast cancer. METHODS: Our institutional database was queried for patients with preoperative mammography and breast MR imaging. RESULTS: There were 573 women eligible for analysis. Elevated BMI was associated with advanced stage of disease (P=.01), lower mammographic density (P<.0001), lower FGT (P<.0001), higher BPE (P=.005), and nonpalpable lesions (P=.04). CONCLUSIONS: Higher BMI was associated with decreased breast density and FGT. Higher BMI was also associated with advanced stage disease and nonpalpable tumors on clinical exam.

Dietary fish intake and sleep quality: a population-based study.

BACKGROUND/OBJECTIVES: Due to the content of omega-3 and vitamin D, fish consumption is likely to be associated with better sleep. However, current data are limited to a single study that is not representative of the population at large. The present study aimed to assess the effects of oily fish consumption on sleep quality in community dwelling adults living in rural coastal Ecuador. METHODS: Atahualpa residents aged ≥40 years and who were identified during a door-to-door survey were interviewed with field instruments directed at assessing cardiovascular risk factors, sleep quality, and fish consumption. Using parametric regression and generalized linear models adjusted for demographics and cardiovascular risk factors, the study evaluated whether oily fish consumption is associated with a lower Pittsburgh sleep quality index (PSQI). RESULTS: Out of 721 eligible people, 677 (94%) were enrolled. Mean oily fish consumption was 9 ± 6 servings per week (one serving = 140 grams). Poor sleep quality was noticed in 187 (28%) individuals. Oily fish intake was higher in individuals with good sleep quality (p = 0.013). There was an inverse association between the PSQI score and oily fish servings per week in both parametric regression (ß = -0.040; 95% CI -0.690 to -0.011, p = 0.007) and the adjusted generalized linear model (ß = -0.032; 95% CI -0.605 to -0.004, p = 0.025). CONCLUSIONS: Oily fish consumption is associated with better sleep quality. Even in people who ingest more than the recommended amount of fish, an increase in fish intake is associated with further improvement in the quality of sleep.

Calcifications in the carotid siphon correlate with silent cerebral small vessel disease in community-dwelling older adults: A population-based study in rural Ecuador.

AIM: Using a population-based, cross-sectional design, we aimed to assess whether the presence of calcifications in the carotid siphon (as seen on computed tomography) is associated with silent markers of cerebral small vessel disease (on magnetic resonance imaging) in apparently healthy older adults living in Atahualpa, a rural Ecuadorian village. METHODS: Stroke-free Atahualpa residents aged ≥60 years identified during a door-to-door survey underwent head computed tomography for assessment of carotid siphon calcifications, and brain magnetic resonance imaging for identification of white matter hyperintensities and silent lacunar infarcts. We evaluated the association between calcifications and markers of small vessel disease using logistic regression models adjusted for demographics and cardiovascular risk factors. RESULTS: The mean age of the 236 participants was 71 ± 8 years, and 139 (59%) were women. Computed tomography readings showed high calcium content in the carotid siphon in 64 individuals (27%), and magnetic resonance imaging showed moderate-to-severe white matter hyperintensities in 51 (30%) and lacunar infarcts in 28 (12%). In the univariate analysis, individuals with high calcium content were older and were more likely to have high fasting glucose levels than those with low calcium content. After adjusting for confounding variables, we found an independent association between high calcium content in the carotid siphon and moderate-to-severe white matter hyperintensities (OR 2.3, 95% CI 1.1-4.9, P = 0.035) as well as lacunar infarcts (OR 3.1, 95% CI 1.3-7.6, P = 0.013). CONCLUSIONS: The present study shows a direct relationship between calcium content in the carotid siphon and silent small vessel disease in an indigenous Latin American population. Geriatr Gerontol Int 2016; 16: 1063-1067.

Dietary Oily Fish Intake and Blood Pressure Levels: A Population-Based Study.

The effect of fish consumption on blood pressure is controversial. The authors measured blood pressure and calculated oily fish servings per week in 677 community-dwellers aged 40 years and older living in rural coastal Ecuador. Using regression models with linear splines, the authors evaluated whether dietary fish intake was related to blood pressure levels, after adjusting for relevant confounders. Mean oily fish consumption was 9.1±5.6 servings per week. There was a nonlinear relationship between systolic pressure and fish servings. In the group of individuals consuming up to five servings per week, each serving significantly reduced systolic pressure by 2.3 mm Hg (P=.020). Any extra serving provided no further effects. The study shows an inverse relationship between oily fish consumption and systolic pressure. Currently recommended amounts of dietary oily fish intake per week (1-2 servings) might be insufficient to exert beneficial effects of fish in the control of blood pressure.

Teaching Translational Research to Medical Students: The New York University School of Medicine's Master's of Science in Clinical Investigation Dual-Degree Program.

To develop the next generation of translational investigators, New York University School of Medicine (NYUSOM) and the NYU-NYC Health and Hospitals Corporation Clinical and Translational Science Institute (NYU-HHC CTSI) developed the Master's of Science in Clinical Investigation dual-degree (MD/MSCI) program. This 5-year program dedicates 1 year to coursework and biomedical research, followed by a medical school/research overlap year, to prepare students for academic research careers. This paper details the MD/MSCI program's curriculum and approach to mentorship, describes the research/professional interests of students, and reports student productivity. In the first 4 years of the program (2010-2014) 20 students were matriculated; 7 (35%) were women, and 12 (60%) research projects were in surgical specialties. To date, 14 students have applied to residency, and half pursued surgical residency programs. Our students have produced 68 accepted abstracts, 15 abstracts in submission, 38 accepted papers, and 24 papers in submission. Despite the time-limited nature of this program, additional training in research design and implementation has promoted a high level of productivity. We conclude that dual-degree training in medicine and translational research is feasible for medical students and allows for meaningful participation in valuable projects. Follow-up is warranted to evaluate the academic trajectory of these students.

The role of dynamic contrast-enhanced screening breast MRI in populations at increased risk for breast cancer.

Breast MRI is more sensitive than mammography in detecting breast cancer. However, MRI as a screening tool is limited to high-risk patients due to cost, low specificity and insufficient evidence for its use in intermediate-risk populations. Nonetheless, in the past decade, there has been a dramatic increase in the use of breast-screening MRI in the community setting. In this review, we set to describe the current literature on the use of screening MRI in high- and intermediate-risk populations. We will also describe novel applications of breast MRI including abbreviated breast MRI protocols, background parenchymal enhancement and diffusion-weighted imaging.

The role of T1r3 and Trpm5 in carbohydrate-induced obesity in mice.

We examined the role of T1r3 and Trpm5 taste signaling proteins in carbohydrate-induced overeating and obesity. T1r3, encoded by Tas1r3, is part of the T1r2+T1r3 sugar taste receptor, while Trpm5 mediates signaling for G protein-coupled receptors in taste cells. It is known that C57BL/6 wild-type (WT) mice are attracted to the tastes of both Polycose (a glucose polymer) and sucrose, whereas Tas1r3 KO mice are attracted to the taste of Polycose but not sucrose. In contrast, Trpm5 KO mice are not attracted to the taste of sucrose or Polycose. In Experiment 1, we maintained the WT, Tas1r3 KO and Trpm5 KO mice on one of three diets for 38days: lab chow plus water (Control diet); chow, water and 34% Polycose solution (Polycose diet); or chow, water and 34% sucrose solution (Sucrose diet). The WT and Tas1r3 KO mice overconsumed the Polycose diet and became obese. The WT and Tas1r3 KO mice also overconsumed the Sucrose diet, but only the WT mice became obese. The Trpm5 KO mice, in contrast, showed little or no overeating on the Sucrose and Polycose diets, and gained less weight than WT mice on these diets. In Experiment 2, we asked whether the Tas1r3 KO mice exhibited impaired weight gain on the Sucrose diet because it was insipid. To test this hypothesis, we maintained the WT and Tas1r3 KO mice on one of two diets for 38 days: chow, water and a dilute (1%) but highly palatable Intralipid emulsion (Control diet); or chow, water and a 34% sucrose+1% Intralipid solution (Suc+IL diet). The WT and Tas1r3 KO mice both exhibited little or no overeating but became obese on the Suc+IL diet. Our results suggest that nutritive solutions must be highly palatable to cause carbohydrate-induced obesity in mice, and that palatability produces this effect in part by enhancing nutrient utilization.