Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats

SCH 206272, an antagonist of neurokinin receptors 1, 2, and 3, was administered orally by gavage for 1 month to 8- to 10-month-old dogs at doses of 0, 15, 30, or 60 mg/kg, and to 6-week-old rats at doses of 0, 30, 100, or 300 mg/kg. The most important changes occurred in the reproductive tract of the dogs at all doses. Absolute and relative group mean organ weights for the testes, prostate gland, epididymides, ovaries, and uterus were 33-86% lower than concurrent controls in groups receiving SCH 206272. Organ weight changes were not dose-related. Microscopic changes that correlated with the organ weight changes occurred in all groups receiving SCH 206272. For males, they included minimal to severe atrophy of the testes, epididymides, and prostate gland. In addition, the epididymides exhibited severe oligospermia or aspermia, minimal epithelial apoptosis and mild epithelial vacuolation. In female dogs, the ovaries and uteri appeared immature. Microscopic changes were similar in incidence and severity in dogs receiving 30 or 60 mg/kg, but were slightly less in dogs receiving 15 mg/kg. In contrast, similar findings were not observed in the reproductive tract of male or female rats, despite overlapping systemic, hypothalamic, and pituitary gland concentrations of SCH 206272.     

Human peripheral blood dendritic cells and monocyte subsets display similar chemokine receptor expression profiles with differential migratory responses

Human antigen presenting cells (APC) found in peripheral blood are considered to be precursors that have been released from the bone marrow and are in transit to the peripheral tissues. These APC populations include myeloid dendritic cells (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional roles and stages of development for APCs, CD33 expressing APC subsets were examined for their capacity to respond to chemokines. Three major CD33(+) subsets including CD33(bright)CD14(bright) Mo, CD33(bright)CD14(-) CD11c(+) mDC and CD33(dim)CD14(-) pDC were present. Dendritic cells subsets and Mo expressed low levels of CC and CXC receptors, but distinctive chemokine receptor expression profiles were not observed. The percentage of cells expressing a particular chemokine receptor varied from donor to donor and over time in the same donor. Myeloid DC and Mo but not pDC migrated toward CXCL12 in a concentration dependent manner. Monocytes and pDC, but not myeloid DC, were attracted by high concentrations of CXCL10. All CD33(+) subsets migrated in a concentration dependent manner toward CCL19, but responded less robustly to CCL21. CCL20 was not chemoattractant for any population. Despite the finding that APC did not exhibit unique surface chemokine receptor expression patterns, they exhibited differential migration to CXCL12, CXCL10 and CCL21 but not to CCL20 or CCL19.     

Prostate brachytherapy seed reconstruction using an adaptive grouping technique

Fluoroscopy-based three-dimensional seed localization as a component of intraoperative dosimetry for prostate brachytherapy is an active area of research. A novel adaptive-grouping-based reconstruction approach is developed. This approach can recover overlapped seeds that are not detected from the fluoroscopic images. Two versions of the adaptive-grouping-based reconstruction approach are implemented and compared to an epipolar geometry-based seed reconstruction technique. Simulations based on nine patient datasets are used to validate the algorithms. A total of 2259 reconstructions is performed in which different types of error such as random noise in seed image locations and ambiguities in projection geometry are incorporated. Among those reconstructions, nine of the cases with overlapping seeds and the different types of error are performed. It is demonstrated that the adaptive-grouping-based reconstruction method is more accurate than the epipolar geometry method and allows faster reconstruction. At a random noise level of 0.6 mm, the mean distance error in reconstructed seed locations is approximately 1.0 mm for one of the relevant cases examined in detail. The best adaptive-grouping-based approach successfully recovered overlapped seeds in the majority of simulated cases (89%), with the remainder of cases generating one false positive seed. Phantom validation is also performed, and overlapped seeds are successfully recovered with all 92 seeds correctly localized and reconstructed. The mean distance error between segmented seed images and projected seeds is 0.5 mm in the phantom study.     

Comparison of hydrogenated vegetable shortening and nutritionally complete high-fat diet on limited access-binge behavior in rats

Previous studies have suggested that intermittent exposure to hydrogenated vegetable shortening yields a binge/compensate pattern of feeding in rats. The present study was designed to assess whether rats would exhibit similar patterns of intake when given intermittent access to a nutritionally complete high-fat diet. Four groups of rats received varying exposure to either hydrogenated vegetable shortening or high-fat diet for 8 consecutive weeks. Animals were given daily and intermittent access to determine if the binge/compensate pattern of feeding was frequency dependent. At the conclusion of the study, body composition and plasma leptin levels were assessed to determine effects of diet and binge/compensate intake on endocrine alterations. As predicted, animals receiving intermittent access to high-fat diet displayed the binge/compensate pattern of feeding and appeared to compensate as a result of the caloric overload accompanying a particular binge episode. In addition, exposure to either shortening or high-fat diet led to alterations in body composition, while only exposure to shortening altered plasma leptin levels. These results suggest that binge-intake behavior occurs on a nutritionally complete high-fat diet and that this regimen is capable of altering both body composition and endocrine profile.     

Influencing medical student choice of primary care worldwide: international application of the four pillars for primary care physician workforce

Primary care is a crucial part of a functional health care system, though in many parts of the world there are current or projected gaps in the primary care physician workforce. The academic family medicine organizations in the United States (US) developed the “Four Pillars for Primary Care Physician Workforce,” a model built on decades of research, highlighting four main areas of emphasis for increasing primary care physician output: 1) pipeline; 2) process of medical education; 3) practice transformation; and 4) payment reform. This commentary proposes that this model, although developed in the US context, is applicable in other medical education settings, including Israel, based on the recently reported findings of Weissman and colleagues in this journal.