Long-term persistence of piscine orthoreovirus-1 (PRV-1) infection during the pre-smolt stages of Atlantic salmon in freshwater.

Piscine orthoreovirus (PRV) causes heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. During salmon production cycles, HSMI has predominantly been observed after seawater transfer. More recently, better surveillance and longitudinal studies have detected occurrences of PRV-1 in freshwater broodstock farms and hatcheries. However, very little is known about the viral kinetics of PRV-1 or disease development of HSMI during these pre-smolt stages. In this study, we conducted a long-term PRV-1 challenge experiment to examine the profile of viral load, infectiousness and/or clearance in Atlantic salmon during their development from fry to parr stage. Atlantic salmon fry (mean weight: 1.1 ± 0.19 g) were infected with PRV-1 (high virulent variant) via intraperitoneal (IP) injection. The viral load reached a peak at 2-4 weeks post-challenge (wpc) in heart and muscle tissues. The virus was detected at relatively high levels in whole blood, spleen, and head kidney tissues until 65 wpc. Heart and muscle lesions typical of HSMI were clearly observed at 6 and 8 wpc but then subsided afterwards resolving inflammation. Innate and adaptive immune responses were elicited during the early/acute phase but returned to basal levels during the persistent phase of infection. Despite achieving high viremia, PRV-1 infection failed to cause any mortality during the 65-week virus challenge period. Cohabitation of PRV-1 infected fish (10 and 31 wpc) with naïve Atlantic salmon fry resulted in very low or no infection. Moreover, repeated chasing stress exposures did not affect the viral load or shedding of PRV-1 at 26 and 44 wpc. The present findings provide knowledge about PRV-1 infection in juvenile salmon and highlight the importance of continued monitoring and management to prevent and mitigate the PRV-1 infection in freshwater facilities.

Atlantic salmon post-smolts adapted for a longer time to seawater develop an effective humoral and cellular immune response against Salmonid alphavirus.

Salmonid alphavirus (SAV) causes pancreas disease (PD) in Atlantic salmon (Salmo salar L.) and disease outbreaks are mainly detected after seawater transfer. The influence of the smoltification process on the immune responses, specifically the adaptive response of Atlantic salmon after SAV infection, is not fully understood. In this study, Atlantic salmon post-smolts were infected by either bath immersion (BI) or intramuscular injection (IM) with SAV subtype 3, 2 weeks (Phase A) or 9 weeks (Phase B) after seawater transfer. The transcript levels of genes related to cellular, humoral and inflammatory responses were evaluated on head kidney samples collected at 3, 7, 14, 21, and 28 days post-infection (dpi). Corresponding negative control groups (CT) were established accordingly. Significant differences were found between both phases and between the IM and BI groups. The anti-inflammatory cytokine IL-10 was up-regulated in Phase A at a higher level than in Phase B. High mRNA levels of the genes RIG-1, SOCS1 and STAT1 were observed in all groups except the BI-B group (BI-Phase B). Moreover, the IM-B group showed a higher regulation of genes related to cellular responses, such as CD40, MHCII, and IL-15, that indicated the activation of a strong cell-mediated immune response. CD40 mRNA levels were elevated one week earlier in the BI-B group than in the BI-A group (BI-Phase A). A significant up-regulation of IgM and IgT genes was seen in both IM groups, but the presence of neutralizing antibodies to SAV was detected only in Phase B fish at 21 and 28 dpi. In addition, we found differences in the basal levels of some of the analysed genes between non-infected control groups of both phases. Findings suggest that Atlantic salmon post-smolts adapted for a longer time to seawater before they come into contact with SAV, developed a stronger humoral and cell-mediated immune response during a SAV infection.

A large drawing of a nephron for teaching medical students renal physiology, histology, and pharmacology.

The purpose of this study is to see whether a large drawing of a nephron helped medical students in self-directed learning groups learn renal physiology, histology, and pharmacology before discussing clinical cases. The end points were the grades on the renal examination and a student survey. The classes in the fall of 2014 and 2015 used the drawing, but not those of 2012 and 2013. The Charles E. Schmidt College of Medicine at Florida Atlantic University is a newly formed Florida medical school, which enrolled its first class in the fall of 2011. The school relies on self-directed problem-based learning in year 1 and changes over to a case inquiry method in the latter part of year 1 and throughout year 2. At the start of the renal course, each student group received a poster of a nephron with the objective of learning the cell functions of the different nephron parts. During the first year of using the drawing, there was no improvement in grades. After a student suggested adjustment to the drawing, there was a statistically significant difference in the total test score in the second year ( P < 0.001). An unexpected finding was lower grades in all 4 yr in the area of acid-base balance and electrolytes compared with the other four areas tested. In the survey, the students found the drawing useful.

Atlantic salmon adapted to seawater for 9 weeks develop a robust immune response to salmonid alphavirus upon bath challenge.

Pancreas disease (PD) caused by salmonid alphavirus (SAV) is the most serious viral disease in Norwegian aquaculture. Study of the immune response to SAV will aid preventative measures including vaccine development. The innate immune response was studied in Atlantic salmon infected by either bath immersion (BI) or by intra-muscular (i.m.) injection (IM) with SAV subtype 3, two and nine weeks after seawater transfer (Phases A and B respectively). Phase A results have been previously published (Moore et al., 2017) and Phase B results are presented here together with a comparison of results achieved in Phase A. There was a rapid accumulation of infected fish in the IM-B (IM Phase B) group and all fish sampled were SAV RNA positive by 7 dpi (days post infection). In contrast, only a few SAV RNA positive (infected) fish were identified at 14, 21 and 28 dpi in the BI-B (BI Phase B) group. Differences in the transcription of several immune genes were apparent when compared between the infected fish in the IM-B and BI-B groups. Transcription of the analysed genes peaked at 7 dpi in the IM-B group and at 14 dpi in the BI-B group. However, this latter finding was difficult to interpret due to the low prevalence of SAV positive fish in this group. Additionally, fish positive for SAV RNA in the BI-B group showed higher transcription of IL-1ß, IFNγ and CXCL11_L1, all genes associated with the inflammatory response, compared to the IM-B group. Histopathological changes in the heart were restricted to the IM-B group, while (immune) cell filtration into the pancreas was observed in both groups. Compared to the Phase A fish that were exposed to SAV3 two weeks after seawater transfer, the Phase B fish in the current paper, showed a higher and more sustained innate immune gene transcription in response to the SAV3 infection. In addition, the basal transcription of several innate immune genes in non-infected control fish in Phase B (CT-B) was also significantly different when compared to Phase A control fish (CT-A).

High-Temperature and High-Energy-Density Dipolar Glass Polymers Based on Sulfonylated Poly(2,6-dimethyl-1,4-phenylene oxide).

A new class of high-temperature dipolar polymers based on sulfonylated poly(2,6-dimethyl-1,4-phenylene oxide) (SO2 -PPO) was synthesized by post-polymer functionalization. Owing to the efficient rotation of highly polar methylsulfonyl side groups below the glass transition temperature (Tg ≈220 °C), the dipolar polarization of these SO2 -PPOs was enhanced, and thus the dielectric constant was high. Consequently, the discharge energy density reached up to 22 J cm-3 . Owing to its high Tg , the SO2 -PPO25 sample also exhibited a low dielectric loss. For example, the dissipation factor (tan δ) was 0.003, and the discharge efficiency at 800 MV m-1 was 92 %. Therefore, these dipolar glass polymers are promising for high-temperature, high-energy-density, and low-loss electrical energy storage applications.

Immune gene profiles in Atlantic salmon (salmo salar L.) post-smolts infected with SAV3 by bath-challenge show a delayed response and lower levels of gene transcription compared to injected fish.

Salmonid alphavirus (SAV) causes pancreatic disease (PD) in salmonids in Northern Europe which results in large economic losses within the aquaculture industry. In order to better understand the underlying immune mechanisms during a SAV3 infection Atlantic salmon post-smolts were infected by either i.m.-injection or bath immersion and their immune responses compared. Analysis of viral loads showed that by 14 dpi i.m.-injected and bath immersion groups had 95.6% and 100% prevalence respectively and that both groups had developed the severe pathology typical of PD. The immune response was evaluated by using RT-qPCR to measure the transcription of innate immune genes involved in the interferon (IFN) response as well as genes associated with inflammation. Our results showed that IFNa transcription was only weakly upregulated, especially in the bath immersion group. Despite this, high levels of the IFN-stimulated genes (ISGs) such as Mx and viperin were observed. The immune response in the i.m.-injected group as measured by immune gene transcription was generally faster, and more pronounced than the response in the bath immersion group, especially at earlier time-points. The response in the bath immersion group started later as expected and appeared to last longer often exceeding the response in the i.m-injected fish at later time-points. High levels of transcription of many genes indicative of an active innate immune response were present in both groups.

Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p < 0.05). These findings suggest that airway inflammation occurs after an HFM when exercise is performed in the postprandial period, regardless of habitual activity level.

Discussion: "Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties" (Rowland, E. M., Mohamied, Y., Chooi, K. Y., Bailey, E. L., and Weinberg, P. D., 2015, ASME J. Biomech. Eng., 137(10), p. 101003): An Alternative Approach Using Segmentation Based on Local Hemodynamics.

The biological response of living arteries to mechanical forces is an important component of the atherosclerotic process and is responsible, at least in part, for the well-recognized spatial variation in atherosusceptibility in man. Experiments to elucidate this response often generate maps of force and response variables over the arterial surface, from which the force-response relationship is sought. Rowland et al. discussed several statistical approaches to the spatial autocorrelation that confounds the analysis of such maps and applied them to maps of hemodynamic stress and vascular response obtained by averaging these variables in multiple animals. Here, we point out an alternative approach, in which discrete surface regions are defined by the hemodynamic stress levels they experience, and the stress and response in each animal are treated separately. This approach, applied properly, is insensitive to autocorrelation and less sensitive to the effect of confounding hemodynamic variables. The analysis suggests an inverse relation between permeability and shear that differs from that in Rowland et al. Possible sources of this difference are suggested.

Atlantic salmon (Salmo salar L.) post-smolts challenged two or nine weeks after seawater-transfer show differences in their susceptibility to salmonid alphavirus subtype 3 (SAV3).

BACKGROUND: Pancreas disease (PD), caused by salmonid alphavirus (SAV), is an important disease affecting salmonid aquaculture. It has been speculated that Atlantic salmon post-smolts are more prone to infections in the first few weeks following seawater- transfer. After this period of seawater acclimatization, the post-smolts are more robust and better able to resist infection by pathogens. Here we describe how we established a bath immersion (BI) model for SAV subtype 3 (SAV3) in seawater. We also report how this challenge model was used to study the susceptibility of post-smolts to SAV3 infection in two groups of post-smolts two weeks or nine weeks after seawater - transfer. METHODS: Post-smolts, two weeks (Phase-A) or nine weeks (Phase-B) after seawater- transfer, were infected with SAV3 by BI or intramuscular injection (IM) to evaluate their susceptibility to infection. A RT-qPCR assay targeting the non-structural protein (nsP1) gene was performed to detect SAV3-RNA in blood, heart tissue and electropositive-filtered tank-water. Histopathological changes were examined by light microscope, and the presence of SAV3 antigen in pancreas tissue was confirmed using immuno-histochemistry. RESULTS: Virus shedding from the Phase-B fish injected with SAV3 (IM Phase-B) was markedly lower than that from IM Phase-A fish. A lower percentage of viraemia in Phase-B fish compared with Phase-A fish was also observed. Viral RNA in hearts from IM Phase-A fish was higher than in IM Phase-B fish at all sampling points (p < 0.05) and a similar trend was also seen in the BI groups. Necrosis of exocrine pancreatic cells was observed in all infected groups. Extensive histopathological changes were found in Phase-A fish whereas milder PD-related histopathological lesions were seen in Phase-B fish. The presence of SAV3 in pancreas tissue from all infected groups was also confirmed by immuno-histochemical staining. CONCLUSION: Our results suggest that post-smolts are more susceptible to SAV3 infection two weeks after seawater-transfer than nine weeks after transfer. In addition, the BI challenge model described here offers an alternative SAV3 infection model when better control of the time-of-infection is essential for studying basic immunological mechanisms and disease progression.

Environmental Predictors of Unmet Home-and Community-Based Service Needs of Older Adults.

Home- and community-based services (HCBS) for many older adults are an essential component of aging-in-place. Andersen developed the contemporary model used to predict service use. Researchers have modified the model to examine need. Studies that attempt to predict unmet needs have explained only 10% to 15% of the variance. This study is based on the supposition that lack of accounting for environmental factors has resulted in such small explanatory power. Through the use of 2008 Southeastern Pennsylvania Household Health Survey data, this exploratory study modeled predictors of unmet HCBS needs. Findings reveal that lack of access to healthy foods and poor housing quality have a significant relationship to unmet HCBS needs. This model predicted 54% of the variance. Results reveal environmental questions to ask, a way to identify older adults with unmet HCBS needs and environmental barriers that if addressed may reduce older adults' eventual need for health services and HCBS.

Cerebral Blood Flow Velocity During Combined Lower Body Negative Pressure and Cognitive Stress.

BACKGROUND: Lower body negative pressure (LBNP) decreases middle cerebral artery blood velocity (MCAv) and can induce hypotension. Mental stress increases MCAv, but the MCAv response to combined LBNP and mental stress (COMBO) is unknown. We hypothesized that performing a stressful cognitive challenge (i.e., mental stress) concurrently with LBNP would prevent LBNP-induced reductions of MCAv. METHODS: There were 18 subjects (9 men, 9 women; ages 20.1±0.3 yr) who completed 3 randomized 3-min trials: 1) LBNP (-40 mmHg); 2) mental stress (serial subtraction); and 3) COMBO (LBNP+mental stress). All reported values are mean±SE. Mean arterial pressure (MAP), heart rate (HR), forearm blood flow (FBF), and MCAv were measured continuously. Subjects also reported perceived stress following the mental stress and COMBO trials. RESULTS: LBNP decreased MAP (Δ-1.4±0.5 mmHg), MCAv (Δ-2.6±1.1 cm s(-1)) and FBF (Δ-0.8±0.1 units), and increased HR (Δ2.7±1.2 bpm). Mental stress increased MAP (Δ10.1±1.3 mmHg), HR (Δ17.4±2.2 bpm), and FBF (Δ2.4±0.4 units), while MCAv (Δ2.8±1.3 cm s(-1)) tended to increase. COMBO increased MAP (Δ5.3±2.3 mmHg) and HR (Δ21.3±2.6 bpm), and tended to increase FBF (Δ0.5±0.3 units). However, MCAv (Δ-4.6±2.0 cm s(-1)) decreased during COMBO. Decreases in MCAv during COMBO were not statistically different from LBNP-induced decreases (Δ-4.6±2.0 vs. Δ-2.6±1.1 cm s(-1)). Subjective ratings of perceived stress (standard 0 to 4 scale) tended to be higher during COMBO than mental stress (2.9±0.1 vs. 2.5±0.1 units). CONCLUSION: Our results suggest that mental stress does not effectively preserve MCAv when combined with central hypovolemia (i.e., LBNP).

Casualties of war: the infection control assessment of civilians transferred from conflict zones to specialist units overseas for treatment.

The casualties of global conflict attract media attention and sympathy in public, governmental, and non-governmental circles. Hospitals in developed countries offering specialist reconstructive or tertiary services are not infrequently asked to accept civilian patients from overseas conflict for complex surgical procedures or rehabilitation. Concern about the infection prevention and control risks posed by these patients, and the lack of a good evidence base on which to base measured precautions, means that the precautionary principle of accepting zero risk is usually followed. The aim of this article is to highlight infection control considerations that may be required when treating casualties from overseas conflict, based partly on our own experience. Currently there is a lack of published evidence and national consensus on how to manage these patients. The precautionary principle requires that there is an ongoing search for evidence and knowledge that can be used to move towards more traditional risk management. We propose that only by gathering the experiences of the many individual hospitals that have each cared for small numbers of such patients can such evidence and knowledge be assimilated.

The frequency of spontaneous triploidy in farmed Atlantic salmon produced in Norway during the period 2007-2014.

BACKGROUND: Spontaneous triploidy has been reported in a number of fish species, and is often linked with in vivo or in vitro ageing of eggs post ovulation. Here, we provide the first investigation into the frequency of spontaneous triploidy in farmed Atlantic salmon by analysing more than 4000 fish from 55 farms, and approximately 1000 recaptured escapees, all sampled in the period 2007-2014. In addition, we compare microsatellite genotyping against flow cytometry and red blood cell diameter in a set of 45 putatively diploid and 45 putatively triploid Atlantic salmon. RESULTS: The three methods implemented for ploidy determination gave consistent results, thus validating the methods used here. Overall, 2.0% spontaneous triploids were observed in salmon sampled on farms. The frequency of spontaneous triploids varied greatly among sea cages (0-28%), but they were observed in similar frequencies among the three primary breeding companies (1.8-2.4%). Spontaneous triploids were observed in all farming regions in Norway, and in all years sampled. Spontaneous triploids were also observed among the escapees recaptured in both the marine environment and in rivers. CONCLUSIONS: Spontaneous triploidy in commercially produced Atlantic salmon is likely to be a result of the practices employed by the industry. For logistical reasons, there is sometimes a pause of hours, and in some cases overnight, between killing the female broodfish, removal of her eggs, and fertilization. This gives the eggs time to age post ovulation, and increases the probability of duplication of the maternal chromosome set by inhibition of the second polar body release after normal meiosis II in the oocyte.

Achieving high dielectric constant and low loss property in a dipolar glass polymer containing strongly dipolar and small-sized sulfone groups.

In this report, a dipolar glass polymer, poly(2-(methylsulfonyl)ethyl methacrylate) (PMSEMA), was synthesized by free radical polymerization of the corresponding methacrylate monomer. Due to the large dipole moment (4.25 D) and small size of the side-chain sulfone groups, PMSEMA exhibited a strong γ transition at a temperature as low as -110 °C at 1 Hz, about 220 °C below its glass transition temperature around 109 °C. Because of this strong γ dipole relaxation, the glassy PMSEMA sample exhibited a high dielectric constant of 11.4 and a low dissipation factor (tan δ) of 0.02 at 25 °C and 1 Hz. From an electric displacement-electric field (D-E) loop study, PMSEMA demonstrated a high discharge energy density of 4.54 J/cm(3) at 283 MV/m, nearly 3 times that of an analogue polymer, poly(methyl methacrylate) (PMMA). However, the hysteresis loss was only 1/3-1/2 of that for PMMA. This study suggests that dipolar glass polymers with large dipole moments and small-sized dipolar side groups are promising candidates for high energy density and low loss dielectric applications.