Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres: expert practical experience and advice.

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition.This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient's journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue.

PURPOSE: Chronic fatigue (CF) affects 25-30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. METHODS: This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. RESULTS: Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. CONCLUSION: Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www. CLINICALTRIALS: gov/ct2/show/NCT04931407.

Metabolic syndrome and risk of incident psoriasis: prospective data from the HUNT Study, Norway.

BACKGROUND: Metabolic syndrome has been associated with psoriasis in cross-sectional studies, but data from prospective studies are sparse. OBJECTIVES: To examine prospectively whether metabolic syndrome and its components are associated with the risk of incident psoriasis in a large population-based study using objective measurements of cardiovascular disease risk factors. METHODS: We used data from two consecutive surveys of the HUNT Study, Norway (HUNT2, 1995-1997, and HUNT3, 2006-2008). In total 34 996 women and men aged ≥ 20 years without psoriasis in HUNT2 were followed up in HUNT3, and 374 incident cases of psoriasis were identified. We used Cox regression to estimate the adjusted relative risk (RR) of incident psoriasis with its 95% confidence interval (CI). RESULTS: Metabolic syndrome was associated with an RR for psoriasis of 1·66 (95% CI 1·30-2·14). To explore the influence of adiposity on this association, we first excluded waist circumference from the definition of metabolic syndrome (adjusted RR 1·54, 95% CI 1·14-2·07) and then adjusted for body mass index (RR 1·33, 95% CI 0·97-1·81). Analyses of the separate components of metabolic syndrome showed positive associations with risk of psoriasis for waist circumference, triglycerides and high-density lipoprotein (HDL) cholesterol, but not for blood pressure or blood glucose. There was also an increased risk of psoriasis for high total cholesterol. The increased risk associated with high triglycerides, HDL cholesterol and total cholesterol was attenuated after adjusting for body mass index. CONCLUSIONS: In this large prospective study from a general population, we found that metabolic syndrome was associated with increased risk of incident psoriasis, and our results suggest that this positive association could, at least partly, be attributed to adiposity.

Predicting reactivity threshold in children with anaphylaxis to peanut.

BACKGROUND: Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. OBJECTIVE: We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. METHODS: A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. RESULTS: During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63+ basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction. CONCLUSION AND CLINICAL RELEVANCE: In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity.

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.

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).

Psoriasis and cardiovascular disease risk factors: the HUNT Study, Norway.

BACKGROUND: Studies have examined the associations between psoriasis and cardiovascular diseases and their risk factors, but the results are conflicting, especially in the general population. OBJECTIVES: To investigate the association of psoriasis, and in particular psoriasis severity, with objectively measured cardiovascular disease risk factors and cardiovascular morbidity in a large population-based cross-sectional study. METHODS: We linked data on 50 245 persons in the HUNT3 Study, Norway, with information from the National Prescription Database to obtain information on use of psoriasis medication. A total of 2894 persons reported to have psoriasis; 2643 were classified as mild; and 251 as moderate/severe psoriasis. We used linear and logistic regression to estimate adjusted associations with 95% confidence intervals (CIs) between psoriasis and cardiovascular disease risk factors and morbidity. RESULTS: We observed a positive association between psoriasis and objective measures of body mass index (BMI), waist circumference and high-sensitivity C-reactive protein, but no clear association with blood pressure and blood lipids. People with moderate/severe psoriasis had an odds ratio for being overweight of 1.94 (95% CI 1.42, 2.67), whereas the odds ratio for metabolic syndrome was 1.91 (95% CI 1.47, 2.49). Psoriasis was also positively associated with self-reported diabetes, myocardial infarction and angina pectoris. CONCLUSIONS: In this population-based study, we found that psoriasis was positively associated with measures of adiposity, as well as with a clustering of cardiovascular disease risk factors. Overall, these associations were strongest for people with moderate/severe psoriasis.

Insomnia and risk of chronic musculoskeletal complaints: longitudinal data from the HUNT study, Norway.

BACKGROUND: The aim of this study was to investigate the prospective association between insomnia and risk of chronic musculoskeletal complaints (CMSC) and chronic widespread musculoskeletal complaints (CWMSC). A second aim was to evaluate the association between insomnia and number of body regions with CMSC at follow-up. METHODS: We used data from the second (HUNT2, 1995-1997) and third (HUNT3, 2006-2008) wave of the Nord-Trøndelag Health Study (the HUNT Study). The population-at-risk included 13,429 people aged 20-70 years who reported no CMSC at baseline in HUNT2 and who answered the questionnaires on insomnia in HUNT2 and CMSC in HUNT3. Insomnia was defined according to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) with minor modification, whereas CMSC was assessed for nine different body regions. CWMSC was defined according to the 1990 criteria by the American College of Rheumatology. We used Poisson regression to estimate adjusted risk ratios (RRs) for CMSC and CWMSC at 11 years follow-up. Precision of the estimates was assessed by a 95% confidence interval (CIs). RESULTS: Insomnia at baseline was associated with increased risk of any CMSC (RR 1.16, 95% CI 1.03-1.32) and CWMSC (RR 1.58, 95% CI 1.26-1.98) at follow-up. RR for CMSC for specific body regions ranged from 1.34 (95% CI 1.05-1.73) for the knees and 1.34 (1.10-1.63) for the neck to 1.60 (95% CI 1.19-2.14) for the ankles/ft. Further, insomnia was associated with increased risk of CMSC in 3-4 regions (RR 1.36, 95% CI 1.05-1.77), and 5 or more regions (RR 1.93, 95% CI 1.40-2.66), but not 1-2 regions (RR 0.99, 95% CI 0.80-1.24). CONCLUSIONS: Insomnia is associated with increased risk of CMSC, CWMSC, and CMSC located in 3 or more body regions.

Genetic factors contribute more to hip than knee surgery due to osteoarthritis - a population-based twin registry study of joint arthroplasty.

OBJECTIVE: To explore and quantify the relative strengths of the genetic contribution vs the contribution of modifiable environmental factors to severe osteoarthritis (OA) having progressed to total joint arthroplasty. DESIGN: Incident data from the Norwegian Arthroplasty Registry were linked with the Norwegian Twin Registry on the National ID-number in 2014 in a population-based prospective cohort study of same-sex twins born 1915-60 (53.4% females). Education level and height/weight were self-reported and Body Mass Index (BMI) calculated. The total follow-up time was 27 years for hip arthroplasty (1987-2014, 424,914 person-years) and 20 years for knee arthroplasty (1994-2014, 306,207 person-years). We estimated concordances and the genetic contribution to arthroplasty due to OA in separate analyses for the hip and knee joint. RESULTS: The population comprised N = 9058 twin pairs (N = 3803 monozygotic (MZ), N = 5226 dizygotic (DZ)). In total, 73% (95% confidence intervals (CI) = 66-78%) and 45% (95% CI = 30-58%) of the respective variation in hip and knee arthroplasty could be explained by genetic factors. Zygosity (as a proxy for genetic factors) was associated with hip arthroplasty concordance over time when adjusted for sex, age, education and BMI (HR = 2.98, 95% CI = 1.90-4.67 for MZ compared to DZ twins). Knee arthroplasty was to a greater extent dependent on BMI when adjusted for zygosity and the other covariates (HR = 1.15, 95% CI = 1.02-1.29). CONCLUSION: Hip arthroplasty was strongly influenced by genetic factors whereas knee arthroplasty to a greater extent depended on a high BMI. The study may imply there is a greater potential for preventing progression of knee OA to arthroplasty in comparison with hip OA.

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.

Water temperature and dietary histidine affect cataract formation in Atlantic salmon (Salmo salar L.) diploid and triploid yearling smolt.

The aim of the present study was to investigate cataract development in diploid (2N) and triploid (3N) Atlantic salmon smolts and post-smolts at two water temperatures (10 and 16 °C) given diets with different histidine supplementation (LH, 10.4 and HH, 13.1 g kg-1 ) before and after seawater transfer. In freshwater, a severe cataract outbreak was recorded in both ploidies reared at 16 °C. The cataract score was significantly higher in triploids compared to diploids, and the severity was lower in both ploidies fed the HH diet. The cataract development at 10 °C was minor. Low gill Na+ , K+ -ATPase activity in fish reared at 16 °C before seawater transfer was followed by osmoregulatory stress with elevated plasma electrolyte concentrations and high mortality in sea water. Both diploids and triploids reared at 10 °C developed cataracts during the seawater period, with higher severities in triploids than diploids and a reduced severity in the fish fed the HH diet. The findings of this study demonstrate the importance of environmental conditions in the husbandry of Atlantic salmon, and particularly triploids, with regard to smoltification and adjusted diets to mitigate cataract development in fresh and sea water.

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.

Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 µm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 µm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.

Leisure-time physical activity and disability pension: 9 years follow-up of the HUNT Study, Norway.

The objective of this study was to prospectively examine the association between leisure-time physical activity and risk of disability pension, as well as risk of disability pension because of musculoskeletal or mental disorders in a large population-based cohort. Data on participants aged 20-65 years in the Norwegian Nord-Trøndelag Health Study 1995-1997 (HUNT2) were linked to the National Insurance Database. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for disability pension across physical activity categories. During a follow-up of 9.3 years and 235,657 person-years, 1266 of 13,823 men (9%) and 1734 of 14,531 women (12%) received disability pension. Compared with individuals in the inactive group, those in the highly active group had a 50% lower risk of receiving disability pension (HR for men: 0.50, 0.40-0.64; women: 0.50, 0.39-0.63). After comprehensive adjustment for potential confounders, the risk remained 32-35% lower (HR for men: 0.68, 0.53-0.86; women: 0.65, 0.51-0.83). The associations were stronger for disability pension due to musculoskeletal disorders than mental disorders. In summary, we observed strong inverse associations between leisure-time physical activity and disability pension. Our findings strengthen the hypothesis that leisure-time physical activity may be important for occupational health in reducing disability pension.

Concentrations of remifentanil, propofol, fentanyl, and midazolam during rewarming from therapeutic hypothermia.

BACKGROUND: The clearance of sedatives and analgesics may be reduced by therapeutic hypothermia. However, little is known about the concentrations of such drugs during rewarming. The aim of this study was to describe the serum concentrations of sedatives and analgesics during rewarming from therapeutic hypothermia. METHODS: Blood samples were collected for quantification of drug concentrations in 22 patients given analgesia/sedation with either remifentanil/propofol or fentanyl/midazolam during rewarming from therapeutic hypothermia (33-34°C) after cardiac arrest. Samples for were drawn before (-2 h) and during rewarming (0-8 h). Linear mixed effects models were used to describe serum concentrations and adjust for rates of infusion during rewarming from therapeutic hypothermia. RESULTS: Subjects with samples analyzed were remifentanil (n = 8), propofol (n = 14), fentanyl (n = 8), and midazolam (n = 8). Age, body mass index, and simplified acute physiology score II [mean (standard deviation)] were 64 (14.2) years, 27.3 (3.7) kg/m(2), and 69 (13.2), respectively. While the concentration of fentanyl was not significantly affected by temperature, concentrations of remifentanil, propofol, and midazolam decreased with core temperature by 16%, 12%, and 11% (mean values) from 33°C to 37°C after adjusting for rates of infusion, respectively. CONCLUSION: Concentrations of remifentanil, propofol, and midazolam decreased during rewarming from therapeutic hypothermia when adjusting for rates of infusion. No changes were demonstrated for fentanyl.

Development of seawater tolerance and subsequent downstream migration in wild and stocked young-of-the-year derived Atlantic salmon Salmo salar smolts.

This study investigated the development of hypo-osmoregulatory capacity and timing of downstream migration in wild Atlantic salmon Salmo salar smolts from the River Stjørdalselva and stocked young-of-the-year (YOY), derived S. salar smolts from the tributary River Dalåa. Both wild and stocked S. salar smolts developed seawater (SW) tolerance in early May, persisting through June, measured as their ability to regulate plasma osmolality and chloride following 24 h SW (salinity = 35) exposure. Although the majority of downstream migration among the stocked S. salar smolts occurred later than observed in their wild counterparts, the development of SW tolerance occurred concurrently. The wild S. salar from Stjørdalselva and stocked YOY smolts from the River Dalåa started to migrate on the same cumulative day-degrees (D°). The study revealed no downstream migration before development of SW tolerance. This emphasizes the importance of incorporating physiological status when studying environmental triggers for downstream migration of S. salar smolts. Overall, these findings suggest that the onset of smolt migration in stocked S. salar smolts was within the smolt window from an osmoregulatory point of view.

Long-term hypo-osmoregulatory capacity in downstream migrating Atlantic salmon Salmo salar L. smolts.

The duration of hypo-osmoregulatory capacity in downstream migrating Atlantic salmon Salmo salar L smolts previously stocked as startfed young-of-the year (YOY) parr was tested in the River Dalåa from mid-May to late-June 1999. Hypo-osmoregulatory capacity, measured as plasma osmolality and chloride, was assessed after seawater (SW) challenge tests (168 h, salinity = 35). All S. salar exhibited sufficient hypo-osmoregulatory capacity at the initiation of downstream migration in mid-May. Migrating S. salar smolts caught in mid-May and retained in fresh water displayed no signs of de-smoltification as they maintained hypo-osmoregulatory capacity through June. This indicates a physiological smolt window that lasts a minimum of 6 weeks (330 degree days; D°) for hatchery-produced S. salar smolts stocked as YOY parr. Based on the observed river migration speeds, it can be assumed that the S. salar smolts entered SW 2-4 weeks after initiation of migration in the upper parts of the River Dalåa. Hence, based on smolt migration and SW tolerance, it is suggested that stocking of YOY parr is a viable enhancement strategy in the River Dalåa.

Development of intestinal ion-transporting mechanisms during smoltification and seawater acclimation in Atlantic salmon Salmo salar.

This study investigated the expression of ion transporters involved in intestinal fluid absorption and presents evidence for developmental changes in abundance and tissue distribution of these transporters during smoltification and seawater (SW) acclimation of Atlantic salmon Salmo salar. Emphasis was placed on Na(+) , K(+) -ATPase (NKA) and Na(+) , K(+) , Cl(-) co-transporter (NKCC) isoforms, at both transcriptional and protein levels, together with transcription of chloride channel genes. The nka α1c was the dominant isoform at the transcript level in both proximal and distal intestines; also, it was the most abundant isoform expressed in the basolateral membrane of enterocytes in the proximal intestine. This isoform was also abundantly expressed in the distal intestine in the lower part of the mucosal folds. The protein expression of intestinal Nkaα1c increased during smoltification. Immunostaining was localized to the basal membrane of the enterocytes in freshwater (FW) fish, and re-distributed to a lateral position after SW entry. Two other Nka isoforms, α1a and α1b, were expressed in the intestine but were not regulated to the same extent during smoltification and subsequent SW transfer. Their localization in the intestinal wall indicates a house-keeping function in excitatory tissues. The absorptive form of the NKCC-like isoform (sub-apically located NKCC2 and/or Na(+) , Cl(-) co-transporter) increased during smoltification and further after SW transfer. The cellular distribution changed from a diffuse expression in the sub-apical regions during smoltification to clustering of the transporters closer to the apical membrane after entry to SW. Furthermore, transcript abundance indicates that the mechanisms necessary for exit of chloride ions across the basolateral membrane and into the lateral intercellular space are present in the form of one or more of three different chloride channels: cystic fibrosis transmembrane conductance regulator I and II and chloride channel 3.

Osmoregulation in Atlantic salmon Salmo salar smolts transferred to seawater at different temperatures.

In order to investigate how changes in gill Na(+) , K(+) -ATPase (NKA) α1a and α1b subunits, Na(+) , K(+) , 2Cl(-) co-transporter (NKCC1) and the apical cystic fibrosis trans-membrane conductance regulator-I (CFTR-I) transcripts in wild strain of Atlantic salmon, Salmo salar, smolts are affected by temperature during spring, hatchery-reared parr (mean ± s.e. fork length = 14·1 ± 0·5; mean ± s.e. body mass = 28·5 ± 4·5 g) originating from broodstock from the Vosso river (western Norway) were acclimated to three temperature regimes (4·1, 8·1 and 12·9° C) in May and reared under gradually increasing salinity between May and June. Changes in plasma Na(+) , haematocrit (Hct) and PCO2 were monitored in order to assess and compare key physiological changes with the transcriptional changes in key ion transporters. The temperatures reflect the natural temperature range in the River Vosso during late spring. Overall, higher gill NKA α1b mRNA levels, gill NKCC1a levels and CFTR-I levels were observed in the 4·1° C group compared to the 11·9° C group. This coincided with a 2-3 week period with decreased Hct and PCO2 and may indicate a critical window when smolts suffer from reduced physical performance during migration. Further research is needed to confirm the potential interaction between ecological and physiological conditions on mortality of hatchery-reared smolts from River Vosso during their natural migration.

Plasma growth hormone-binding protein levels in Atlantic salmon Salmo salar during smoltification and seawater transfer.

Specific growth hormone (GH)-binding protein (Ghbp) was purified from Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss plasma with immunoprecipitation and characterized in cross-linking studies using autoradiography and western blots. The size of the Ghbp was estimated to be c. 53 kDa. A radioimmunoassay was established to measure Ghbp in salmonids, using antibodies specific against the extracellular segment of the S. salar growth hormone receptor 1 (grh1; GenBank AY462105). Plasma Ghbp levels were measured in S. salar smolts in fresh water and after transfer to seawater (SW; experiments 1 and 2), and in post-smolts kept at different salinities (0, 12, 22 and 34) for 3 months (experiment 3). A transient increase in plasma Ghbp, which lasted for 1 month or less, was noted in smolts after transfer to SW. Concomitantly, plasma GH and gill Na(+) -K(+) -ATPase activity increased during smoltification (in experiment 2). No difference in plasma Ghbp was evident between post-smolts kept at different salinities, although the fish kept at salinity 34 had higher plasma GH than the group kept at salinity 22 and higher hepatic ghr1 expression than post-smolts kept at salinity 12. This suggests that plasma Ghbp regulation may respond to salinity changes in the short term. The lack of correlation between Ghbp, plasma GH and hepatic ghr1 expression in the long-term post-smolt experiment indicates that Ghbp levels may be regulated independently of other components of the endocrine GH system in salmonids.