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Background: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins. Patients and Methods: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0–3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins. Results: A total of 631 patients participated. Median age was 64 (range 29–94) years, with a median tumor size of 1.3 cm (range 0.1–9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status. Conclusion: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors. [ABSTRACT FROM AUTHOR]

Kinetic resolution provided a highly enantioselective method to access a range of 3-aryl-3,4-dihydro-2 H -1,4-benzoxazines using n -butyllithium and the chiral ligand sparteine. The enantioenrichment remained high on removing the tert -butoxycarbonyl (Boc) protecting group. The intermediate organolithium undergoes ring opening to an enamine. The kinetic resolution was extended to give enantiomerically enriched substituted 1,2,3,4-tetrahydroquinoxalines and was applied to the synthesis of an analogue of the antibiotic levofloxacin that was screened for its activity against the human pathogen Streptococcus pneumoniae. [ABSTRACT FROM AUTHOR]

In advanced age, there is an accelerated decline in skeletal muscle mass that appears to be secondary to repeated cycles of denervation-reinnervation and eventually, failed reinnervation. However, whether variation in reinnervation capacity explains why some muscles are less vulnerable to age-related atrophy has not been addressed. In this study we examined changes in neuromuscular junction (NMJ) morphology, fiber cross-sectional area (CSA) and fiber type, accumulation of severely atrophied myofibers, and expression of a marker of denervation in four muscles that exhibit differences in the degree of age-related atrophy and which span the extremes of fiber type composition in 8 mo old (8 M) and 34 mo old (34 M) male Fischer 344 Brown Norway F1 hybrid rats. Aging muscle atrophy was most pronounced in the fast twitch gastrocnemius (Gas; 25%) and similar between extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscle (14–15%), whereas the slow-twitch adductor longus (AL) increased in mass by 21% between 8 M and 34 M (P < 0.05 for all). Only the Sol exhibited significant alterations in fiber type with aging, and there was a decrease in fiber CSA in the Gas, EDL, and Sol (P < 0.05) with aging that was not seen in the AL. Muscles that atrophied had an increased fraction of severely atrophic myofibers (P < 0.05), but this was not observed in the AL. The Gas and EDL both demonstrated a similar degree of age-related remodeling of pre- and post-synaptic NMJ components. On the other hand, pre- and post-synaptic morphology underwent greater changes with aging in the AL, and many of these same morphological variables were already greater in the Sol vs AL at 8 M, suggesting the Sol had already undergone substantial remodeling and may be nearing its adaptive limits. Consistent with this idea, analysis of NMJ morphology in Sol from 3 M rats exhibited similar values as 8 M AL, and the Sol demonstrated greater expression of the denervation marker neural cell adhesion molecule (NCAM) compared to the AL at 34 M. Collectively, our results are consistent with NMJ remodeling capacity being finite with aging and that maintained remodeling potential confers atrophy protection in aging skeletal muscle by reducing the degree of persistent denervation. • Loss of muscle mass in aging is heterogeneous, as some muscles resist atrophy. • We examined the role of the neuromuscular junction in susceptibility to aging muscle atrophy. • Neuromuscular junction remodeling appears to be finite. • Muscle exhibiting greater neuromuscular junction remodeling earlier in lifespan exhibits greater denervation in advanced age. • Conversely, maintained neuromuscular junction remodeling capacity with aging appears protective against muscle atrophy. [ABSTRACT FROM AUTHOR]

"Animal-based research should be held to the highest ethical standards" is becoming an increasingly common refrain. Though I think such a commitment is what we should expect of those using animals in science, much as we would if the participants were humans, some key insights of discussions in applied ethics and moral philosophy only seem to slowly impact what reasonably qualifies as the highest standards in animal research ethics. Early in my paper, I will explain some of these insights and loosely tie them to animal research ethics. Two emergent practices in laboratory animal science, positive reinforcement training and "rehoming," will then be discussed, and I will defend the view that both should be mandatory on no more ethical grounds than what is outlined in the first section. I will also provide reasons for foregrounding the moral significance of dissent and why, most of the time, an animal research subject's sustained dissent should be respected. Taken together, what I will defend promises to change how at least some animals are used in science and what happens to them afterwards. But I will also show how an objective ethics requires nothing less. Ignoring these constraints in the scientific use of animals comes at the cost of abandoning any claim to adhering to our highest ethical standards and, arguably, any claim to the moral legitimacy of such scientific use., (© The Author(s) 2020. Published by Oxford University Press on behalf of the National Academies of Sciences, Engineering, and Medicine. All rights reserved. For permissions, please email: journals.permissions@oup.com.)