Circadian regulation of hepatic detoxification seems to be amongst the key roles of the biological clock. The liver is the major site for biotransformation, and in mammals, it contains several ...clock-controlled transcription factors such as proline and acidic amino acid-rich basic leucine zipper proteins (PAR bZIP) and basic-helix-loop-helix Per-Arnt-Sim (bHLH-PAS) family that act as circadian regulators of detoxification genes. This investigation explored the existence of daily and circadian expression of transcription factors involved in detoxification, as well as the temporal profile of a set of their target genes in zebrafish liver. In our study, zebrafish were able to synchronize to a light-dark (LD) cycle and displayed a diurnal pattern of activity. In addition, the expression of clock genes presented daily and circadian rhythmicity in liver. Apart from hlfa, the expression of PAR bZIP transcription factors also displayed daily rhythms, which appeared to be both light-dependent and clock-controlled, as circadian rhythms free-ran under constant conditions (continuous darkness, DD). Under LD, tefb, dbpa and dbpb expression peaked at the end of the darkness period whereas tefa showed peak levels of expression at the onset of the photophase. In addition, these four genes exhibited circadian expression under DD, with higher expression levels at the end of the subjective night. The expression of the bHLH-PAS transcription factor arh2 also showed circadian rhythmicity in zebrafish liver, peaking in the middle of the subjective night and approximately 3-4 h before peak expression of the PAR bZIP genes. Regarding the detoxification genes, the major target gene of AhR, cyp1a, showed daily and circadian expression with an acrophase 2 h after ahr2. Under LD, abcb4 also showed daily rhythmicity, with an acrophase 1-2 h after that of PAR bZIP factors during the transition between darkness and light phases, when zebrafish become active. However, the expression of six detoxification genes showed circadian rhythmicity under DD, including cyp1a and abcb4 as well as gstr1, mgst3a, abcg2 and sult2_st2. In all cases, the acrophases of these genes were found during the second half of the subjective night, in phase with the PAR bZIP transcription factors. This suggested that their expression is clock-controlled, either directly by core clock genes or through transcription factors. This study presents new data demonstrating that the process of detoxification is under circadian control in fish. Results showed that time of day should be considered when designing toxicological studies or administering drugs to fish.
Abstract Background Various factors contribute to instability of total hip arthroplasty (THA), with implant orientation being a major contributor. We performed a case-control study with computed ...tomography (CT) data to determine whether 1) orientation contributes to THA instability and 2) a safer target zone for stability than Lewinnek's classic safe zone can be defined. Material and methods We included prospectively 363 cases of THA dislocation that occurred during the calendar 2013 year in 24 participating hospitals. Of the 128 dislocations that occurred in patients who underwent THA at these centers, 56 (24 anterior, 32 posterior) had CT scans, thus were included in the analysis. The control group was matched 4:1 based on implant type, year of implantation, age, sex, bearing types and THA indication. Of the 428 matched control THA cases, 93 had CT scans. In all, the CT scans from 149 cases (56 unstable, 93 stable) were analyzed to determine the acetabular cup's inclination and anteversion, and the femoral stem's anteversion. Results In the unstable THA group, cup inclination was 46.9° ± 7.4°, cup anteversion was 20.4° ± 10.8° and stem anteversion was 14.2° ± 9.9°. In the stable THA group, cup inclination was 44.9° ± 5.3° (p=0.057), cup anteversion was 22.1° ± 5.1° (p=0.009) and stem anteversion was 13.4° ± 4.4° (p=0.362). The optimal total anteversion (cup + stem) of 40–60° was achieved in 16.5% of unstable THA cases and 13.9% of stable THA cases, thus this parameter does not predict stability (Odds Ratio (OR) of 0.40, p=0.144). The cup was positioned in Lewinnek's safe zone in 44.6% of patients in the unstable group and 68.2% of those in the stablegroup (OR 3.74, p=0.003).A target zone defined as 40–50° inclination and 15–30° anteversion was better able to distinguish between unstable cases (23.2%) and stable cases (71.6%) resulting in an OR of 13.91 (p<0.001). Discussion Implant positioning was the only risk factor for instability found in this study.Moreover, our findings reinforce the theory put forward by other authors that Lewinnek's safe zone is not specific enough to differentiate between stable and unstable THA implantations. The target zone for acetabular cups proposed here (40–50° inclination and 15°–30° anteversion) is relatedto a lower risk of instability. This orientation can be used as a guide, but must be combined with other technical elements to optimize stability. By balancing stability and biomechanics, the 40–50° inclination and 15°–30° anteversion target zone redefines the optimal positioning window. Level of evidence IIIcase-control study
Diploid (2N) and triploid (3N) sibling post-smolts were divided between six sea pens and fed: a standard commercial nutrient package diet (2×2N SP, 2×3N SP), or an iso-energetic nutrient boosted ...(higher dietary protein and phosphorous) package (2×3N BP) until market size. 3N groups initially grew significantly faster than 2N, and by harvest, 3N BP weighed significantly more (3210±87g) than 2N SP or 3N SP (3007±64g; 2965±88g), while there was no significant difference in weight between ploidy in SP diet. Higher visible vertebral (9.6±0.4%) and jaw deformities (10.6±1.2%) were observed in 3N compared to 2N (0.9±0.1%; 1.3±0.5%). However, x-ray radiography revealed that 3N BP and 2N SP had comparable levels of severely affected individuals at time of sea transfer, while 3N SP showed a 3 fold increase in the severity of malformed individuals. The tail region (R3) in 3N SP fish had both the lowest vertebral strength and stiffness and the highest number of deformed vertebrae. Fillet quality attributes were comparable between diet and ploidy. These findings show that triploid growth rate can be sustained until harvest throughout the seawater phase, and more importantly the progression of spinal deformity beyond that at sea transfer can be stabilised by increasing dietary P during the marine phase.
Tailored triploid specific aquafeeds must be formulated to support growth and prevent deformity in order to minimise welfare implications and allow exploitation of faster growth potential of triploid salmon within industry.
•Triploid Atlantic salmon growth rate can be sustained during marine rearing using protein enriched diets•Severity of skeletal deformity can be reduced by feeding nutrient enriched diets•Occurrence of skeletal deformity in triploid Atlantic salmon must be addressed during freshwater stages in the first instance
Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known.
We performed a retrospective multicenter cohort study that involved patients with total hip/knee ...prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009.
Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04).
The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients.
Ballan wrasse (Labrus bergylta) aquaculture has emerged as a strategic development for the sustainable control of sea-lice (Lepeophtheirus salmonis) in the European Atlantic salmon (Salmo salar) ...industry. Farmed ballan wrasse juveniles were exposed to a standard acute stressor (1min air exposure) and the patterns of change in blood haematocrit, plasma cortisol, glucose and lactate were described over a 24h period using newly validated analytical methods in that species. Plasma cortisol concentrations were relatively high and rose from a resting basal level of 60.8±5.5ng·ml−1 to a peak concentration of 284.3±26.7ng·ml−1 (3.7-fold increase) 30min post stress exposure. Cortisol was found to be the most sensitive indicator of stress followed by plasma glucose showing 83.9% increase from a resting basal level of 2.2±0.1mmol·l−1 30min post-stressor. The use of handheld metres for monitoring glucose and lactate levels was successfully validated against the reference spectrophotometric methods for on-site assessment. Validation of the methods and identification of the most sensitive stress indicators are expected to assist in the identification of adverse conditions and best rearing practices for this emerging new aquaculture species.
•Blood haematocrit, plasma cortisol, glucose and lactate were measured in farmed ballan wrasse exposed to an acute stressor.•Basal plasma cortisol levels were high and cortisol response to air exposure relatively low compared to other fish species.•Handheld meters for monitoring glucose and lactate levels were successfully validated.•The methods and indicators validated are expected to assist in identifying best rearing practices for this emerging species.
Using sterile triploid salmon is of interest to fish farmers as a means to mitigate interbreeding between farmed and wild fish, prevent pre-harvest maturation and offer potential for faster growth. ...We investigated within the same experiment whether growth, deformity and cataract prevalence in diploid and triploid Atlantic salmon post-smolts (8 full-sib families) were influenced by isolated- or mixed-ploidy rearing during 12months of sea water grow-out in tanks until harvest. Diploids attained significantly higher harvest weights than triploids in both treatments (+6.7% isolated, +26.3% mixed). Triploid harvest weight was 29.6% lower under mixed ploidy rearing than their isolated triploid siblings. A similar effect was also observed in diploids (12% lower harvest weight). Family had a significant effect on harvest weight in both ploidy. However, family harvest weight in triploids showed a linear relationship between isolated and mixed rearing (r2=0.76), while a non-linear relationship was found between diploids reared in isolation or mixed populations (r2=0.88). Furthermore diploid family weight correlated positively with triploid weight in isolation (r2=0.65), but a non-significant relationship was observed under mixed rearing (r2=0.49). Diploids had a significantly higher condition (K) factor at harvest than triploids in both treatments, while triploid K factor was significantly reduced by mixed rearing with diploids. Triploids had a significantly higher incidence of cataract than diploids in both treatments (60.9–77.3% vs. 21.7–47.2%, severity≥1). However, severity of cataract was greater in both triploids (2.43) and diploids (1.44) grown in isolation than those grown in a mixed ploidy population (triploid 2.17; diploid 1.09). Triploids had a significantly higher prevalence of visible deformity than diploids (18.1 vs. 7.2%), however, triploids grown in isolation had significantly higher prevalence than triploids under mixed rearing (30.4 vs. 5.8%). Collectively, the results provide clear evidence that triploids perform very differently when reared in the presence or absence of diploid conspecifics. Furthermore, observations of reduced deformity and cataract in the slower growing mixed populations support the hypothesis that such malformations are in part a function of higher growth rate. The results of this study also indicate that care should be taken when designing conventional common garden experiments to evaluate family performance between ploidy as interactions between ploidy may influence growth traits, although family effects appear to remain consistent.
•Triploid salmon growth is negatively affected by communal ploidy rearing at sea•Malformation in both ploidy appears to be a function of faster growth rate•Genotype influences prevalence of deformity
This paper describes a study in which environmental manipulation of salmon swimming depth was tested in an attempt to reduce farm infection of Atlantic salmon, Salmo salar by the salmon louse, ...Lepeophtheirus salmonis. The effects of submerged artificial lighting (positioned at 10m depth) in combination with submerged feeding (delivered at 5m depth) were tested with respect to salmon swimming depth and sea lice infection, following the hypothesis that L. salmonis infection in a commercial salmon population is reduced when exposed to deep lighting and feeding. This is based on two assumptions, firstly that planktonic L. salmonis larvae principally remain in surface waters (top 4m) and secondly, that deep lighting and feeding attract salmon to deeper water depths. Results from commercial scale trials confirmed that salmon swimming behaviour is altered under submerged feeding conditions with fish attracted to the feeding corridor during the feeding process. When the fish reached satiation or feeding ceased, they returned to the surface waters during the day. Submerged lighting attracted the fish to the illuminated water depths during the night. During the day, natural light overruled these effects to some extent. The number of L. salmonis on fish exposed to deep submerged lighting was significantly lower than the number of lice found on salmon in cages with surface lighting during the summer months. Submerged feeding showed no advantage over surface feeding with respect to the number of L. salmonis found in these trials. The results of the study suggest that swimming depth manipulation can be used at a commercial scale to reduce salmon lice burdens on Atlantic salmon stocks.
•The study explores the manipulation of feeding and lighting in salmon to control sea lice.•Swimming behaviour is altered by submerged feeding to attract fish to a deeper feed corridor.•Swimming behaviour is altered by submerged lights to attract fish to deeper water layers.•Both regimes aimed at minimising fish-parasite interactions.•Sea louse numbers on the fish were significantly reduced by the trial treatments.
Atypical Aeromonas salmonicida (aAs) and Vibrionaceae related species are bacteria routinely recovered from diseased ballan wrasse used as cleaner fish in the Atlantic salmon farming industry. ...Autogenous (i.e. farm specific inactivated) multivalent vaccines formulated from these microorganisms are widely used to protect farmed wrasse despite limited experimental proof that they are primary pathogens. In this study, the components of a commercial multivalent injection vaccine containing four strains of Aeromonas salmonicida and one strain of Vibrio splendidus previously isolated from ballan wrasse in Scotland, were tested for infectivity, pathogenicity and virulence via intra peritoneal injection at pre-deployment size (25–50 g) and the efficacy of the vaccine for protection against aAs assessed. Injection with 3.5 × 109, 8 × 109 1.8 × 109 and 5 × 109 cfu/fish of Vibrio splendidus, V. ichthyoenteri, Aliivibrio logeii and A. salmonicida, respectively, did not cause significant mortalities, lesions or clinical signs after a period of 14 days. IP injection with both aAs and Photobacterium indicum successfully reproduced the clinical signs and internal lesions observed during natural outbreaks of the disease. Differences in virulence (LD50 at day 8-post infection of 3.6 × 106 cfu/fish and 1.6 × 107 cfu/fish) were observed for two aAs vapA type V isolates. In addition, the LD50 for Photobacterium indicum was 2.2 × 107 cfu/fish. The autogenous vaccine was highly protective against the two aAs vapA type V isolates after 700-degree days of immunisation. The RPSFINAL values for the first isolate were 95 and 91% at 1 × 106 cfu/fish and 1 × 107 cfu/fish, respectively, and 79% at 1 × 107 cfu/fish for the second isolate tested. In addition, significantly higher anti aAs seral antibodies (IgM), were detected by ELISA in vaccinated fish in contrast with control (mock vaccinated) fish. These results suggest wrasse can be effectively immunised and protected against aAs infection by injection with oil adjuvanted vaccines prepared with inactivated homologous isolates.
•Intraperitoneal challenge model developed for ballan wrasse against Aeromonas salmonicida vapA type V.•Vaccine provided high protection in ballan wrasse against homologous aAs vapA type V strains (RPS 79–95%).•Specific serum antibodies (IgM) were detected in vaccinated fish.
Abstract Management of bone loss is a major challenge in revision total knee arthroplasty (TKA). The development of preformed porous tantalum cones offers new possibilities, because they seem to have ...biological and mechanical qualities that facilitate osseointegration. Compared to the original procedure, when metaphyseal bone defects are too severe, a single tantalum cone may not be enough and we have developed a technique that could extend the indications for this cone in these cases. We used 2 cones to fill femoral bone defects in 7 patients. There were no complications due to wear of the tantalum cones. Radiological follow-up did show any migration or loosening. The short-term results confirm the interest of porous tantalum cones and suggest that they can be an alternative to allografts or megaprostheses in case of massive bone defects.
Joint aspiration is currently the reference standard test for diagnosing periprosthetic joint infection (PJI) despite the high rate of false-negative results, of which a major cause is the fastidious ...nature of some microorganisms. A rapid diagnostic test that detects alpha defensin (Synovasure™, Zimmer, Warsaw, IN, USA) in joint fluid can provide the diagnosis of PJI within a few minutes across the full spectrum of causative organisms (including mycobacteria and yeasts). Its performance in detecting bacterial infections is unaltered by concomitant antibiotic therapy. Few studies of Synovasure™ have been conducted by groups that were involved in designing the test, which has not been validated in France. Assessments in referral centres where complex microbiological situations are common hold considerable interest. The objective of this prospective study was to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and causes of error of Synovasure™ used to diagnose periprosthetic infection in complex microbiological situations.
The rapid diagnostic test Synovasure™ has greater than 90% NPV for detecting periprosthetic infections in complex microbiological infections.
Synovasure™ was used 42 times in 39 patients between October 2015 and October 2017 in challenging microbiological situations discordant joint aspiration results (n=20), negative cultures with clinical or laboratory evidence of infection, (n=21), and concomitant antibiotic therapy (n=1). Of the 39 patients, 23 had total knee prostheses, 13 total hip prostheses, and 3 total femoral prostheses. The reference standard to which the Synovasure™ results were compared was the PJI criteria set developed by the Musculoskeletal Infection Society (MSIS).
Synovasure™ was negative in 30 cases with negative joint fluid cultures (30/42, 71.4%). Of the 12 (28.6%) cases with positive Synovasure™ results, only 7 (7/12, 58.3%) had positive joint fluid cultures. According to the MSIS criteria 9 cases were infected, including 8 with positive and 1 with negative Synovasure™ results. Of the 33 cases that were not infected according to MSIS criteria, 29 had negative and 3 positive Synovasure™ results; the remaining case had a positive Synovasure™ result but was excluded when metallosis was found intra-operatively. NPV was 96.7%, PPV 72.7%, sensitivity 88.9%, and specificity 90.6%.
The high NPV of Synovasure™ suggests a role for this test in microbiologically complex situations as a new tool for ruling in and, most importantly, ruling out infection in doubtful cases.
III, prospective study of diagnostic accuracy.
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