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Background Various intestinal morphological alterations have been reported in cultured fish fed diets with high contents of plant ingredients. Since 2000, salmon farmers have reported symptoms indicating an intestinal problem, which we suggest calling lipid malabsorption syndrome (LMS), characterized by pale and foamy appearance of the enterocytes of the pyloric caeca, the result of lipid accumulation. The objective of the present study was to investigate if insufficient dietary choline may be a key component in development of the LMS. Results The results showed that Atlantic salmon ( Salmo salar ), average weight 362 g, fed a plant based diet for 79 days developed signs of LMS. In fish fed a similar diet supplemented with 0.4% choline chloride no signs of LMS were seen. The relative weight of the pyloric caeca was 40% lower, reflecting 65% less triacylglycerol content and histologically normal gut mucosa. Choline supplementation further increased specific fish growth by 18%. The concomitant alterations in intestinal gene expression related to phosphatidylcholine synthesis ( chk and pcyt1a ), cholesterol transport ( abcg5 and npc1l1 ), lipid metabolism and transport ( mgat2a and fabp2 ) and lipoprotein formation ( apoA1 and apoAIV ) confirmed the importance of choline in lipid turnover in the intestine and its ability to prevent LMS. Another important observation was the apparent correlation between plin2 expression and degree of enterocyte hyper-vacuolation observed in the current study, which suggests that plin2 may serve as a marker for intestinal lipid accumulation and steatosis in fish. Future research should be conducted to strengthen the knowledge of choline’s critical role in lipid transport, phospholipid synthesis and lipoprotein secretion to improve formulations of plant based diets for larger fish and to prevent LMS. Conclusions Choline prevents excessive lipid accumulation in the proximal intestine and is essential for Atlantic salmon in seawater.

Inhibitors of bacterial virulence is suggested to be a promising strategy in the fight against bacterial resistance. The zinc metalloproteases (MPs) thermolysin (TLN), pseudolysin (PLN, LasB) and aureolysin (ALN) are bacterial virulence factors from the M4 family of proteases structurally resembling human zinc MPs. Knowledge about the binding modes of substrates and inhibitors with the bacterial and human zinc MPs is therefore fundamental for developing inhibitors without strong off-target effects. In the present paper, we studied the molecular interactions and cleavage of TLN, the prototype enzyme of the M4 family, with the substrate Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp)-OH (ES005) by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and molecular dynamics (MD) simulations. Enzyme inhibition kinetic studies were used to test 5 compounds (H-1 - H-5) containing phosphinyl as the zinc binding group for their inhibition of TLN, PLN and ALN and of the human matrix metalloproteases MMP-9 and MMP-14. The MALDI-TOF MS results revealed that TLN cleaves ES005 at three sites. The most abundant cleavages were between Ala and Phe, and between Gly and Phe, while the third was between Ser and Ala. MD simulations with Ala or Gly in the S 1 subpocket and Phe in S 1 ’ subpocket gave stable interactions between ES005 and TLN. The MD simulations with Ser in the S 1 subpocket and Ala in the S 1 ’ subpocket showed larger movements of the substrate relative to the catalytic site than the others, which may explain that the Ser-Ala cleavage product was less abundant than the cleavage products from Ala-Phe and Gly-Phe. H-1 inhibited MMP-14 and MMP-9 with inhibition constants ranging from 0.89 to 30 μM but did not inhibit the bacterial zinc MPs. Induced fit docking showed that the aromatic group of H-1, that entered the S 1 ’ subpocket of the human MMPs, is too big for the S 1 ’ subpocket of the bacterial zinc MPs. H-2 inhibited the human MMPs with inhibition constants ranging from 0.53 μM (MMP-9) to 3.0 μM (MMP-14) and the bacterial zinc MPs with inhibition constants ranging from 2.5 μM (TLN) to 80 μM (ALN). Induced fit docking indicated that H-2 interacted quite differently with the human and bacterial zinc proteases, but with primed and unprimed subpockets in both. H-3, H-4 and H-5 did not inhibit any of the zinc MPs with inhibition constants < 100 μM. The MD simulations of ES005 with TLN showed that the MALDI-TOF MS results could be explained by that a Phe in S 1 ’ subpocket generate more stable interaction with TLN than an Ala in that subpocket. The docking studies indicated that the size of the S 1 ’ subpocket is an important determinant for inhibitor selectivity between bacterial and human zinc MPs.

Background Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites. Methods Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment. Discussion Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination. Trial registration ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018.

Choline was recently established as an essential nutrient for Atlantic salmon at all life stages. Choline deficiency is manifested as an excessive accumulation of dietary fat within the intestinal enterocytes, a condition known as steatosis. Most of today's plant-based salmon feeds will be choline-deficient unless choline is supplemented. Choline's role in lipid transport suggests that choline requirement may depend on factors such as dietary lipid level and environmental temperature. The present study was therefore conducted to investigate whether lipid level and water temperature can affect steatosis symptoms, and thereby choline requirement in Atlantic salmon. Four choline-deficient plant-based diets were formulated differing in lipid level of 16, 20, 25 and 28 % and fed to salmon of 25 g initial weight in duplicate tanks per diet at two different environmental temperatures: 8 and 15 °C. After 8 weeks of feeding, samples of blood, tissue and gut content from six fish per tank were collected, for analyses of histomorphological, biochemical and molecular biomarkers of steatosis and choline requirement. Increasing lipid level did not affect growth rate but increased relative weight and lipid content of the pyloric caeca and histological symptoms of intestinal steatosis and decreased fish yield. Elevation of the water temperature from 8 to 15 °C, increased growth rate, relative weight of the pyloric caeca, and the histological symptoms of steatosis seemed to become more severe. We conclude that dietary lipid level, as well as environmental temperature, affect choline requirement to a magnitude of importance for fish biology and health, and for fish yield.

Splenic artery embolization (SAE) in the presence of contrast blush (CB) has been recommended to reduce the failure rate of nonoperative management. We hypothesized that the presence of CB on computed tomography has minimal impact on patient outcomes. A retrospective review was conducted of all children (<18 years) with blunt splenic trauma over a 10-year period at a level 1 pediatric trauma center. Data are presented as mean ± standard error of mean. Seven hundred forty children sustained blunt abdominal trauma, of which 549 had an identified solid organ injury. Blunt splenic injury was diagnosed in 270 of the 740 patients. All patients were managed nonoperatively without SAE. CB was seen on computed tomography in 47 patients (17.4%). There were no significant differences in the need for blood transfusion (12.5% vs 11.1%) or length of stay (3.1 vs 3.3 days) or need for splenectomy when compared in children with or without CB. Pediatric trauma patients with blunt splenic injuries can be safely managed without SAE and physiologic response and hemodynamic stability should be the primary determinants of appropriate management.

Background Shoulder impingement syndrome is one of the most common causes of shoulder pain, accounting for approximately 30% of all shoulder pain. Approximately 35% of patients with shoulder impingement syndrome are refractory to conservative treatment. For patients who fail conservative treatment, there is no established treatment to successfully treat their chronic pain. Prior randomized control trials have demonstrated efficacy for the use of a single lead intramuscular peripheral nerve stimulation of the axillary nerve at the motor points of the deltoid muscle for treatment of hemiplegic shoulder pain. This is the first controlled trial to utilize the same novel technology to treat shoulder impingement syndrome outside of the stroke population. Methods This is a dual-site, placebo-controlled, double-blinded, randomized control trial. Participants will be randomized to two treatment groups. The intervention group will be treated with active peripheral nerve stimulation of the axillary nerve of the affected shoulder and the control group will be treated with sham peripheral nerve stimulation of the axillary nerve of the affected shoulder. Both groups will receive a standardized exercise therapy program directed by a licensed therapist. Discussion This study protocol will allow the investigators to determine if this novel, non-pharmacologic treatment of shoulder pain can demonstrate the same benefit in musculoskeletal patients which has been previously demonstrated in the stroke population. Trial registration Clinicaltrials.gov, NCT03752619 . Registered on 26 November 2018.

ObjectiveThe objective of this study was to finalise the development of the Young Disability Questionnaire (YDQ-spine) to measure the consequences of neck, midback and low back pain, relevant for schoolchildren aged 9–12 years.DesignA cross-sectional field test of the YDQ-spine was carried out.SettingDanish primary schools.ParticipantsChildren aged 9–12 years from all Danish schools were invited to complete the questionnaire.MethodsEight hundred and seventy-three schools were invited to participate. Consenting schools received information material, instructions and a link to an electronic version of the prefinal YDQ-spine. Local teachers distributed the electronic YDQ-spine to children aged 9–12 years. Descriptive statistics and item characteristics were carried out. Item reduction was performed using partial interitem correlations (scrutinising correlations>0.3) and factor analyses (items loading>0.3 were retained) to eliminate redundant items and to obtain insight into the structure of the questionnaire.ResultsA total of 768 children from 20 schools answered of the questionnaire and 280 fulfilled the inclusion criteria of having back and/or neck pain (36%). Multisite pain was reported by 38%. Partial interitem correlations and factor analyses resulted in elimination of four items which were considered redundant leaving 24 items in the final YDQ-spine with an optional section on what matters most to the child. The factor analyses showed a two-factor structure with a physical component (13 items) and a psychosocial component (10 items) in addition to one standalone item (sleep).ConclusionThe YDQ-spine is a novel questionnaire with satisfactory content validity measuring physical and psychosocial components (including sleep disturbances) of spinal pain in children aged 9–12 years. It also offers an optional section on what matters most to the child allowing targeted care in clinical practice.

Purpose Demand for Environmental Product Declarations (EPDs) is already high and increasing in the construction and building sectors. The overall purpose of EPDs is comparability of product environmental performance, and they are thus developed in accordance with product category rules (PCRs): requirements and guidelines for how to make EPDs for one or more product groups. Since several organisations publish PCRs, there is a risk of creating conflicting rules leading to inconsistencies and jeopardising the objective of comparability. Methods This study analyses the causes for inconsistency and the consequences in terms of difference in the results across the life cycle assessment (LCA) models underlying the EPDs. Taking four EPD programmes and their actors as cases, first a document analysis was conducted to identify qualitative and quantitative differences in their guidelines. Further focusing on selected quantitative differences, a series of LCA models were designed for the same triple-glazed window product by adhering to the PCRs of each operator, to highlight the differences in results that occur when performing the same assessment via different but all formally selectable operators and compliant EPDs. Results and discussion Results show that the EPD of a specific product can return very different impact scores if one or the other guideline is followed. Results can vary more than 10% from the base scenarios, what we consider a significant variation. This is observed across all impact categories. Focusing specifically on the climate change impact, the results show that differences are due to the choice of energy mix, reference service life and other parameters. It is thus the combination of several modelling differences that leads to a overall divergence in results, rather than one single methodological choice. Conclusions Numerous different but at the same time compliant EPDs can be obtained for the same product, highlighting a serious harmonisation issue within the EPD system. EPDs are thus not necessarily accurate, and it remains doubtful whether EPD comparability can be achieved. This weakness of the EPD system can in the worst case be exploited by producers to obtain lower results and undermines the system. Recommendations Besides recommending using LCA for learning and process improvement rather than just for external communication and compliance, to increase harmonisation in the EPD system, we recommend limiting the number of product-specific PCRs (e.g. complementary PCRs), align default values, learn from verification, use just one background database, increase transparency and move towards one centralized operator.