The Effect of High Dose Total Body Irradiation on ACTH, Corticosterone, and Catecholamines in the Rat

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production

Introduction to Racial Inequity as a Systemic Risk: Why Investors Should Care and How They Can Take Action

This report outlines how the financial industry can manage the systemic risk of racial inequity and promote the equitable distribution of resources, power, and economic opportunity across all races and ethnicities in the U.S. – to advance racial justice and to protect their bottom lines.The report was developed in partnership with TIIP's Racial Equity Working Group. It recommends how investors can leverage conventional investment techniques and more advanced approaches to manage the risks of racial inequity and embed racial equity across portfolios

Forebrain Origins of Glutamatergic Innervation to the Rat Paraventricular Nucleus of the Hypothalamus: Differential Inputs to the Anterior Versus Posterior Subregions

The hypothalamic paraventricular nucleus (PVN) regulates numerous homeostatic systems and functions largely under the influence of forebrain inputs. Glutamate is a major neurotransmitter in forebrain, and glutamate neurosignaling in the PVN is known to mediate many of its functions. Previous work showed that vesicular glutamate transporters (VGluTs; specific markers for glutamatergic neurons) are expressed in forebrain sites that project to the PVN; however, the extent of this presumed glutamatergic innervation to the PVN is not clear. In the present study retrograde FluoroGold (FG) labeling of PVN-projecting neurons was combined with in situ hybridization for VGluT1 and VGluT2 mRNAs to identify forebrain regions that provide glutamatergic innervation to the PVN and its immediate surround in rats, with special consideration for the sources to the anterior versus posterior PVN. VGluT1 mRNA colocalization with retrogradely labeled FG neurons was sparse. VGluT2 mRNA colocalization with FG neurons was most abundant in the ventromedial hypothalamus after anterior PVN FG injections, and in the lateral, posterior, dorsomedial, and ventromedial hypothalamic nuclei after posterior PVN injections. Anterograde tract tracing combined with VGluT2 immunolabeling showed that 1) ventromedial nucleus-derived glutamatergic inputs occur in both the anterior and posterior PVN; 2) posterior nucleus-derived glutamatergic inputs occur predominantly in the posterior PVN; and 3) medial preoptic nucleus-derived inputs to the PVN are not glutamatergic, thereby corroborating the innervation pattern seen with retrograde tracing. The results suggest that PVN subregions are influenced by varying amounts and sources of forebrain glutamatergic regulation, consistent with functional differentiation of glutamate projections. J. Comp. Neurol. 519:1301–1319, 2011. © 2010 Wiley-Liss, Inc

A closer look into empathy among medical students: The career eulogy as a lens

Background Empathy is widely considered to be key to being an effective physician. The measurement of empathy is important to those designing medical education. The majority of the literature on empathy is based on survey scales that ask the learner to express their degree of agreement with a series of statements. We have previously studied and published an entirely projective measure that we term a career eulogy. Methods We had 65 students based at a regional rural medical school campus complete measures of a career eulogy (CE) and the Jefferson Scale of Empathy (JSE) over their four years in medical school. We then calculated weighted correlations between these two instruments. We also asked students to rank 10 factors that they thought affected student responses about empathy. Results We found a significant moderate correlation of JSE score with mentions of compassion on the CE (r = 0.414, p= 0.001). We also found that women scored higher on both instruments. The only factor showing consensus among students was that the general outlook on life was the most likely factor explaining student empathy responses. Conclusions Mentions in the compassion category on the CE appear to be measuring a concept very similar to empathy on the JSE. Students expressed that factors affecting their responses about empathy are very individual and that only interventions to change the general outlook on life may affect these measures of empathy. Having used the CE for the last five years, we find it to be a brief, very useful exercise both for measurement of empathy and as a group facilitation method in our professional identity curriculum. We welcome others to use our CE instrument in larger and more diverse groups to determine its true value in both measuring empathy and facilitating group process

Restraint-induced Corticosterone Secretion and Hypothalamic CRH mRNA Expression are Augmented During Acute Withdrawal from Chronic Cocaine Administration

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus were measured using in situ hybridization and glucocorticoid receptor (GR) protein expression in the pituitary gland and dissected brain regions was measured using Western blot analysis. Basal CRH mRNA in the PVN was unaltered as a result of prior cocaine administration. However, a significant increase in CRH mRNA was observed 90 min following the termination of restraint in cocaine withdrawn, but not saline-treated, rats. Basal CORT was also unaffected by prior cocaine administration, but the CORT response measured immediately after restraint was significantly augmented in cocaine-withdrawn rats. Differences in GR protein expression in number of regions implicated in negative feedback regulation of HPA function, including the hypothalamus, were not observed. These findings indicate that the HPA response to stressors is intensified during early withdrawal from cocaine administration and may be independent of changes in GR-mediated negative feedback

Rural Medical Student Opinions About Rural Practice: Does Choice of College Make a Difference?

Purpose While many programs assume medical students who attended rural colleges are more likely to practice in smaller towns later, there are few studies to support this assumption. This study examines aspects of medical students’ opinions about rural living and rural practice based on where they attended college. Method Students with rural upbringing were identified and administered a previously published rural health opinion survey. The opinion survey was administered across three academic years, from 2015 to 2017, and included a total of three scales and nine subscales for analysis. Factor analysis was used to identify the nine subscales. Results Respondents who attended small town colleges tended to have much stronger opinions about the positive aspects of small town living. Small town college attendees also had stronger positive opinions regarding rural practice than their larger college counterparts. Discussion These preliminary data indicate considering a medical school applicants’ choice of college may provide insight into their opinions about future rural practice. Additional research is needed to collect a larger dataset to examine the association of college choice with opinions about rural practice

Do medical residents with rural upbringing show less decline in empathy during training? A report from a rural family medicine residency

Abstract Purpose Our focus in this study was to determine if demographic variables, including specifically rural upbringing, showed any association with a measure of empathy among family medicine residents at a rural site. Methods We surveyed 40 residents annually using the Jefferson Scale of Empathy (JSE) from 2016 to 2020 and compared scores between residents with rural vs urban hometowns. The response rate was 98/99 (99%) of completed survey opportunities. Findings There was no significant difference in JSE scores of rural vs urban residents at baseline, and both groups showed a decline after the PG-1 year. However, the rural-raised residents showed a significantly different rebound after the PG-2 and PG-3 year, with the urban-raised residents actually showing a slight continuing decline (p=.023 and p=.033). Conclusion These preliminary findings among family medicine residents at a rural site suggest that rural background residents might regain empathy better than urban background residents during the course of their training. Further study should validate our findings and address possible explanations, including the importance of cultural concordance with the patient population served. This and other hypotheses will be explored in further studies with focus groups and other contemporaneous measures

W/SiC x-ray multilayers optimized for use above 100 keV

We have developed a new depth-graded multilayer system comprising W and SiC layers, suitable for use as hard x-ray reflective coatings operating in the energy range 100-200 keV. Grazing-incidence x-ray reflectance at E = 8 keV was used to characterize the interface widths, as well as the temporal and thermal stability in both periodic and depth-graded W/SiC structures, whereas synchrotron radiation was used to measure the hard x-ray reflectance of a depth-graded multilayer designed specifically for use in the range E ~150-170 keV. We have modeled the hard x-ray reflectance using newly derived optical constants, which we determined from reflectance versus incidence angle measurements also made using synchrotron radiation, in the range E = 120-180 keV. We describe our experimental investigation in detail, compare the new W/SiC multilayers with both W/Si and W/B4C films that have been studied previously, and discuss the significance of these results with regard to the eventual development of a hard x-ray nuclear line telescope