Effects of Embryonic Arsenic Exposure on Killifish (Fundulus heteroclitus) Growth, Feeding Behavior, and Intestinal Morphology and Cell Types

Arsenic is found as a contaminant of drinking water, rice, and other crops. Epidemiological studies have shown that embryonic exposure to arsenic can cause changes in behavior and reductions in growth, but the mechanisms for these effects are not well understood. So, we were interested in examining potential mechanisms by which arsenic could be affecting growth. Additionally, while many studies have looked at higher levels of arsenic exposure, we wanted to focus on environmentally-relevant levels to see if these concentrations could have lasting consequences on growth, even after the exposure had ended. Killifish (Fundulus heteroclitus) were used as the model organism for this investigation for two reasons. First, they produce a large number of eggs, which can increase statistical power when observing affects over multiple time points. Second, earlier studies have shown effects on developmental processes at arsenic levels similar to human exposures. In rodent or zebrafish models, investigators typically need to use arsenic concentrations that are 100X higher to see similar effects. Thus, killifish were exposed to 0, 10, 50, and 200ppb arsenic (as sodium arsenite) as embryos, and after hatching were reared in clean water until adulthood at 28 weeks. The study was designed to represent a full embryonic/fetal arsenic exposure in utero, and then to examine whether effects persisted, worsened, or resolved into early adulthood. We found that growth, assessed by condition factor (weight/length³), was significantly reduced by 24% in the 200 ppb embryonic exposure groups at 8 weeks, with a dose dependent decrease in the 10 and 50 ppb groups. These trends persisted up to 28 weeks, although variability was much higher. As we had seen similar reductions in growth in a previous embryonic arsenic exposure study that used higher arsenic concentrations, we therefore investigated three potential mechanisms responsible for the growth reduction. First, we analyzed feeding behavior, as it has been found to correlate to amount of nutrient intake. Embryonic arsenic exposure did indeed reduce the percentage of fish initially responding to food and increased the amount of time it took for the fish to start their response, particularly at the 28 week time period. So, one possibility is that arsenic reduces activity or alters olfaction, thus reducing their response to food. The second mechanism examined was whether embryonic arsenic exposure altered the morphology of the intestine, or altered several specific cell types needed for nutrient uptake. There was a slight, but statistically significant reduction in intestinal villus height at 16 weeks, this change did not persist. Intestinal enterocytes and Goblet cell number, as measured by immunohistochemistry, did not change with arsenic concentration or time. However, the number of PCNA-positive intestinal cells, indicating cell proliferation, was reduced in a dose-response manner at all sampling time points. This may indicate that embryonic arsenic exposure permanently altered the ability of intestinal stem cells to proliferate. The third possibility we examined was whether embryonic arsenic exposure altered the expression of skeletal and hepatic insulin like growth factor (IGF-1), its receptor (IGFR-1) on skeletal muscle cells, and its associated binding proteins (IGFBP-1 & -5) in the muscle and liver. We hypothesized that changes in their levels might alter growth and muscle body weight, since epidemiological studies have found an inverse relationship between arsenic and IGF-1 in plasma levels, which correlate to reductions in birth weight. Reductions of hepatic IGF1 and IGFBP-1 are highly correlated with condition factor reductions in the 8 week old fish. However, by 28 weeks, hepatic IGF-1 and IGFBP-1 still remain tightly correlated, but are actually increased in a statistically significant, dose-response manner. This might be a compensatory response to potentially making up for any growth deficits seen in earlier stages. Overall, the results from this study show that embryonic-only arsenic exposure can alter growth factor expression, such as hepatic IGF-1, which correlates with a reduction in condition factor during an essential growth period such as the juvenile stage. As the fish reach sexual maturity, it appears that by increasing levels of IGF-1 and restoring a consistent intestinal environment, they are able to compensate for early growth deficits after embryonic exposure to lower levels of arsenic

New graduate nurse transition into practice : psychometric testing of Sims Factor H Assessment Scale

Indiana University-Purdue University Indianapolis (IUPUI)Factor H is a newly identified phenomenon which describes a constellation of attributes of the new graduate nurse reflecting personality traits, intellectual abilities, and clinical judgment. In a previous pilot study conducted by this researcher nurse managers and experienced Registered Nurse (RN) preceptors described characteristics demonstrated by new graduate nurses demonstrating Factor H and the new graduate nurse’s ability to transition quickly and successfully into the RN role in the acute care environment. There is currently no instrument available to measure this phenomenon. The specific aim of this research was to develop and psychometrically test a scale designed to identify the presence of attributes of Factor H in the new graduate nurse. The Sims Factor H Assessment Scale (SFHAS) was developed and piloted with a sample of one hundred one new graduate nurses within three months of completing the their nursing program at one of three nursing schools in central and south central Indiana. Evidence of content validity was demonstrated through the use of the Content Validity Index conducted with a panel of four experts. Evidence of face validity was demonstrated through interviews with a group of new graduate nurses, nurse managers, and experienced RN preceptors. Principle Axis Factoring with Varimax rotation was used to demonstrate evidence of construct validity and the scale was found to have a single component which was identified as nursing personality. Evidence of criterion-related validity was demonstrated utilizing analysis of the SFHAS and the criterion scale for personality traits (NEO-FFI). Evidence of internal consistency reliability was demonstrated through analysis of inter-item correlations, Cronbach’s coefficient correlations, and item-total correlations. Test re-test reliability using interclass correlation was also conducted to demonstrate stability of the scale. The SFHAS was found to be reflective of nursing personality and not general mental ability or clinical judgment. Use of the SFHAS will allow organizations to evaluate the nursing personality of the new graduate nurse for fit into the work environment. Further study is recommended to gain clarity around the attributes which support successful transition of the new graduate nurse into practice in the acute care environment, also known as Factor H

Creating a Professional Development Plan for a Simulation Consortium

As the United States struggles with health care reform and a nursing education system that inadequately prepares students for practice, dramatic advances in educational technology signal opportunities for both academic and practicing nurses to affect our profession as never before. Simulation technologies provide large and small institutions with the means to educate health care students and novice professionals effectively and efficiently through hands-on experience, but the costs of such a venture can be prohibitive. A simulation consortium offers a venue for different health care and educational institutions with shared goals to pool knowledge, monies, and labor toward health care education throughout a geographic area. This article details one Midwestern U.S. region's work in creating a professional development plan for a new simulation consortium

The correlation between inflammatory biomarkers and polygenic risk score in Alzheimer's Disease

Plasma biomarkers to aid the early diagnosis of Alzheimer’s disease (AD) or to monitor disease progression have long been sought and continue to be widely studied. Biomarkers that correlate with AD polygenic risk score, a measure of the polygenic architecture of the disease and highly predictive of AD status, would be excellent candidates. Therefore, we undertook a preliminary study to assess the association of plasma inflammatory biomarkers with an overall AD polygenic risk score as well as with an inflammation-specific AD polygenic risk score in a sample set of 93 AD cases. We measured five complement biomarkers [complement receptor 1 (CR1), clusterin, complement component 9 (C9), C1 inhibitor (C1inh), terminal complement complex (TCC)] and the benchmark inflammatory marker C-reactive protein (CRP). Plasma clusterin level showed an association with overall AD polygenic risk score, while clusterin, C1inh, and CRP levels each displayed some association with the inflammatory-specific AD polygenic risk score. The results suggest that elevated plasma levels of inflammatory biomarkers, including complement proteins, associate with polygenic risk scores in AD, further strengthening the link between genetic and biomarker disease predictors and indicating a potential role for these markers in disease prediction and patient stratification in AD

Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Series From a 12-Month Longitudinal Occupational Cohort

Findings are described in 7 patients with severe acute respiratory syndrome coronavirus 2 reinfection from the National Basketball Association 2020-2021 occupational testing cohort, including clinical details, antibody test results, genomic sequencing, and longitudinal reverse-transcription polymerase chain reaction results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response