These experiments confirmed CXCR2 expression on wild-type hepatocytes and neutrophils and no CXCR2 expression on CXCR2 knockout

hepatocytes and neutrophils (data not shown). To exclude the possibility of contamination by genomic DNA, we designed a second pair of primers that crossed exon 1 and exon 2. These experiments confirmed that wild-type hepatocytes and neutrophils expressed CXCR2 (Fig. 7A); CXCR2 knockout hepatocytes selleck chemicals llc did not express any detectable CXCR2. Flow cytometry confirmed these results (Fig. 7B,C). Wild-type hepatocytes expressed low CXCR2 levels. There was no CXCR2 expression on knockout mouse hepatocytes. The mean fluorescence intensity (MFI) of CXCR2 on wild-type hepatocytes (5.26% ± 0.33%) was significantly increased (Fig. 7D) versus knockout mouse hepatocytes (3.42% ± 0.37%, P < 0.05). MFI of hepatocyte CXCR2 expression in wild-type mice 3 hours after APAP dosing was the same as that of untreated hepatocytes, and this suggested that APAP treatment does not change hepatocyte CXCR2 expression in wild-type mice (Fig. 7D). Our results suggest that CXCR2 signaling facilitates apoptosis after APAP dosing. CXCR2

activation requires that CXCR2 ligands, which include KC and MIP2, bind to this receptor. We hypothesized that APAP increases KC and MIP2 production, so hepatic KC and MIP2 protein expression was measured in wild-type and knockout mice after APAP administration by ELISA selleck kinase inhibitor (Fig. 8A,B). KC and MIP2 protein levels increased after APAP and peaked at 4 hours in both wild-type and knockout mice. KC and MIP2 levels in the CXCR2 knockout mice were significantly higher than those in the wild-type mice (P < 0.01) at every time point. These experiments show that CXCR2 knockout mice have a survival advantage over wild-type mice after a median

lethal dose of APAP. The liver injury following APAP in CXCR2 knockout mice is less than that seen in wild-type mice, and this results in significantly selleck chemical lower levels of serum liver enzymes and less liver injury. Further experiments have suggested that this is at least partially related to less apoptosis in knockout mice versus control animals, with no differences in hepatocyte proliferation. However, the role of apoptosis in APAP-induced liver injury is controversial, and it is possible that the less profound GSH depletion seen in this strain of mouse may allow apoptosis to proceed in a more significant fashion than that seen in other models. Although the CXCR2 receptor and its ligands, the CXC chemokines, are known to mediate the inflammatory response, these ligand/receptor interactions also modulate proliferation. For example, Bone-Larson and colleagues demonstrated increased hepatocyte proliferation after APAP injury, which was a CXCR2-dependent response.5 This beneficial proliferative response is dependent on increased CXCR2 expression.5 The CXC chemokines also have a therapeutic role in APAP-induced liver injury.

Habituation in migraineurs has been extensively studied with visual evoked potentials. Despite discrepant results, possibly related to the use of different stimulus conditions, lack of habituation in the period between attacks is presently considered to be a neurophysiological hallmark of migraine. Midoccipital

monocular visual evoked potentials were recorded and analyzed in 27 interictal migraineurs and 34 healthy controls using a blinded study design. Small 8′ checks and large 65′ checks were applied in random order, both with 3 reversals per second. Six consecutive blocks of 100 responses were recorded for each check size. N70-P100 and P100-N145 peak-to-peak amplitudes were measured. Regression slopes across the 6 blocks, supplemented by last block/first block ratio and repeated measures analysis of variance with amplitude as the dependent variable, were used to test for habituation. N70-P100 Stem Cell Compound Library supplier habituation to small and large checks

was observed in controls (mean slope −0.30 and −0.11 μV/block) and interictal migraineurs (−0.32 and −0.26 μV/block). P100-N145 habituation to small checks in controls (mean slope −0.39 μV/block) and to small and large checks in interictal migraineurs (−0.38 and −0.17 μV/block) was also observed. None of the habituation MI-503 molecular weight measures were significantly different between healthy controls and migraineurs (F < 1.6, P > .18). The check-size effect was similar in the 2 groups (F < 2.3, P > .14). Reversal rate and check-size differences do not seem to explain the discrepant visual evoked potential habituation results selleck kinase inhibitor in the migraine literature. Furthermore, no differences in first block amplitudes or N70, P100, and N145 latencies between healthy controls and migraineurs were found. We recommend blinded evaluation designs in future habituation studies in migraine. “
“Migraine has been linked with an increased risk

of stroke and an increased prevalence of clinically silent brain lesions and white-matter hyperintensities. As it is known that stroke and structural brain lesions are associated with an increased risk of cognitive decline, it has been hypothesized that migraine may be a progressive brain disorder and associated with an increased risk of cognitive impairment. Given the prevalence of migraine in the population, especially among women, and the aging of the population, an association between migraine and cognitive impairment would have substantial public health implications. In this review, we will summarize the existing evidence evaluating the association between migraine and cognitive function. Additionally, we will discuss methodological issues in migraine and cognitive function assessment and elaborate on study design strategies to address this important question.

In static stretching, holding each stretch is recommended for 15 [35] or 30 [36–38] s. The number of repetitions varies, with some studies reporting three [36] or four repetitions [38] showing benefits. Sustained increases in ROM have been demonstrated when programmes are performed daily or at least 2–3 times per week [7]. With PNF technique, 1–2 sessions per week are beneficial and even one repetition can acutely increase ROM from 3 to 9 degrees dependent on the joint

[39]. Recommended contraction of the target muscle at a low intensity (20% of maximal contraction) varies between authors at 3–15 s [39]. Unlike the areas of strengthening and aerobic exercise, selleckchem there are no standard, publicized guidelines for participation in stretching activities. As recommended above, these exercises should be incorporated in conjunction with the other elements of musculoskeletal function. Assimilating the research and applying it into clinical practice for those with bleeding disorders requires some consideration and caution. Muscle bleeds are the second most common type of bleeding episode, generally needing more healing time than joint bleeds, with the same ability to negatively impact on ROM. It is advisable to address any ROM limitations after each bleeding episode has resolved. Stretching exercises are a beneficial tool and could be recommended to increase ROM or as a part of an overall fitness regimen.

Care must be taken when initiating stretching following a muscle check details bleed, to begin with very see more light intensity techniques, within the limits of pain and closely monitoring the individual for signs of bleeding. In addition, both ballistic techniques and aggressive passive techniques are potentially dangerous to those with bleeding disorders. Micro-tears of muscle tissue caused through

bouncing while stretching or through aggressive passive techniques could, in fact, lead to further damage. In the presence of chronic synovitis and haemophilic arthropathy with bony changes, the end range limitation of ROM must be respected. Approaching the closed packed position, where the synovium could become impinged or when bony surfaces are coming into contact, should be avoided. There are numerous measurable benefits obtained by performing resistance training exercises, whether by children, adolescent or adult athletic or non-athletic individuals, and regardless of whether they are injured, healthy or have musculoskeletal conditions such as arthritis or haemarthropathy. Some of these benefits include increased muscular strength, endurance and power, as well as improved motor performance and ergonomic tasks, increased cardiovascular fitness, lean body mass and tissue tensile strength including bone mineral density, improved blood lipid profiles, decreased pain and reduced psychological stress [40–54]. In general, the human body responds to various imposed stresses or loads by adaptation.

In static stretching, holding each stretch is recommended for 15 [35] or 30 [36–38] s. The number of repetitions varies, with some studies reporting three [36] or four repetitions [38] showing benefits. Sustained increases in ROM have been demonstrated when programmes are performed daily or at least 2–3 times per week [7]. With PNF technique, 1–2 sessions per week are beneficial and even one repetition can acutely increase ROM from 3 to 9 degrees dependent on the joint

[39]. Recommended contraction of the target muscle at a low intensity (20% of maximal contraction) varies between authors at 3–15 s [39]. Unlike the areas of strengthening and aerobic exercise, Selumetinib datasheet there are no standard, publicized guidelines for participation in stretching activities. As recommended above, these exercises should be incorporated in conjunction with the other elements of musculoskeletal function. Assimilating the research and applying it into clinical practice for those with bleeding disorders requires some consideration and caution. Muscle bleeds are the second most common type of bleeding episode, generally needing more healing time than joint bleeds, with the same ability to negatively impact on ROM. It is advisable to address any ROM limitations after each bleeding episode has resolved. Stretching exercises are a beneficial tool and could be recommended to increase ROM or as a part of an overall fitness regimen.

Care must be taken when initiating stretching following a muscle Gemcitabine bleed, to begin with very selleckchem light intensity techniques, within the limits of pain and closely monitoring the individual for signs of bleeding. In addition, both ballistic techniques and aggressive passive techniques are potentially dangerous to those with bleeding disorders. Micro-tears of muscle tissue caused through

bouncing while stretching or through aggressive passive techniques could, in fact, lead to further damage. In the presence of chronic synovitis and haemophilic arthropathy with bony changes, the end range limitation of ROM must be respected. Approaching the closed packed position, where the synovium could become impinged or when bony surfaces are coming into contact, should be avoided. There are numerous measurable benefits obtained by performing resistance training exercises, whether by children, adolescent or adult athletic or non-athletic individuals, and regardless of whether they are injured, healthy or have musculoskeletal conditions such as arthritis or haemarthropathy. Some of these benefits include increased muscular strength, endurance and power, as well as improved motor performance and ergonomic tasks, increased cardiovascular fitness, lean body mass and tissue tensile strength including bone mineral density, improved blood lipid profiles, decreased pain and reduced psychological stress [40–54]. In general, the human body responds to various imposed stresses or loads by adaptation.

These results indicate that inactivation of ASPP1 and ASPP2 by hypermethylation is a frequent event in the early development of HCC. The ASPP2 gene was found more frequently down-regulated and methylated than the ASPP1 gene in HCC tissues. Moreover, HCCs harboring wildtype p53 more frequently had decreased expression of ASPP2. Knock-down of ASPP2 was more effective in promoting the growth of HCC cells in soft-agar and in nude mice. Thus, ASPP2 might play a more important role in the regulation of tumor development in HCC. ASPP2 was first identified as 53BP2, which contains the C-terminus part of ASPP2.30

The importance of ASPP2 in tumor suppression was recently identified BI 6727 cost in ASPP2-deficient mice.31 ASPP2 heterozygous mice had a 45% tumor incidence over their lifespan, which was three times that in wildtype mice. ASPP2 heterozygous learn more mice also had an increased susceptibility to γ-irradiation-induced tumor development. Besides p53, several proteins have been found to interact with ASPP2, such as Bcl-2, RelA/p65, and hepatitis C virus core protein.32–35 A recent study has found that Drosophila ASPP (dASPP) could interact physically with C-terminal Src kinase (Csk).36 These interactions might contribute to ASPP2-induced cell

survival and proliferation. However, the biological significance of these interactions needs to be explored further. HBx has been found to promote hypermethylation of tumor suppressor genes like find more IGFBP-3 and E-cadherin by activation of DNMTs, and recruitment of DNMTs and methyl-CpG binding proteins to the promoters.21, 23 Recently, HBx was found to have a direct interaction with DNMT3A to regulate gene expression epigenetically.24 It has been found that the methyl-CpG-binding domain (MBD) protein, MBD1, formed a complex with histone H3-K9 methylase SETDB1 and chromatin assembly factor CAF-1 to regulate ASPP2 expression.37 Here we found that ASPP1 and ASPP2 were differentially regulated by HBx. Overexpression

of HBx induced methylation of ASPP2, but not ASPP1. Further analysis revealed that DNMT1 and DNMT3A were recruited to the ASPP2 promoter, but not to the ASPP1 promoter. Thus, the differential regulation of ASPP1 and ASPP2 methylation by HBx might be due to the lacking of DNMTs binding with the ASPP1 promoter. Overexpression of HBx also recruited MeCP2 and MBD1 to the ASPP2 promoter, and released acetylated histone H3 from the ASPP2 promoter. Therefore, HBx might repress ASPP2 expression through regulating the binding of DNMTs and MBD proteins on the ASPP2 promoter. In this study, we demonstrate that methylation-induced ASPP1 and ASPP2 silence play important roles in the development of HCC, which might serve as potent targets for the development of anti-HCC therapy.

6 The predominant literature on NRH is in the form of case reports or small case series and there are

only few reports of portal pressure measurements in this condition. In the current issue of the Journal, Bissonnette et al.8 reported hemodynamic measurements, including HVPG, in 21 patients and portal vein pressure gradient (PVPG, portal vein pressure – inferior vena cava pressure) in 12 patients with NRH. The causes of NRH in these patients included oxaliplatin chemotherapy, treatment with purine antagonists, liver transplantation, hematological and rheumatological conditions, and HIV infection. GSK 3 inhibitor Fifteen out of 21 patients with varices/ascites had HVPG less than 10 mm Hg suggesting a pre-sinusoidal portal hypertension, which was confirmed by a portal vein pressure higher than 12 mm Hg in all 12 patients. Though the majority of patients (15/21) had a pre-sinusoidal component, six patients did have higher HVPG (more

than 10 mm Hg) suggesting sinusoidal portal hypertension.8 These data by Julien et al. thus suggest that both components of portal hypertension (pre-sinusoidal and sinusoidal) occur in patients with NRH. The pre-sinusoidal portal hypertension is related to the well-described vasculopathy (obliterative portal venopathy), while the sinusoidal portal hypertension is probably attributable to sinusoidal obstruction because of compression by regenerative nodules.8 Even though data are sparse, selleck products other studies in patients with NRH have also suggested a mixed type of portal hypertension (pre-sinusoidal and sinusoidal).

click here In one of the case reports, a 47-year-old woman with NRH who underwent HVPG before and after splenectomy had a marked difference between WHVP and FHVP with little difference between portal venous pressure and WHVP; these findings indicated that portal hypertension in NRH was primarily sinusoidal.9 Similar data were shown by two other studies, one another single case report and the other a series of 13 cases.4,10 On the other hand, in a relatively large number of biopsy-proven cases of NRH (n = 14), Arvanitaki and Adler5 suggested that portal hypertension in patients with NRH was pre-sinusoidal. The clinical manifestations included splenomegaly, esophageal varices and variceal bleeding.5 In another recent study, 26 patients receiving 6-thioguanine for inflammatory bowel disease were evaluated with HVPG and liver biopsy.11 Six out of 24 patients (25%) with adequate liver tissue on histology had evidence of NRH. Of six patients with NRH, three had elevated (> 5 mm Hg) HVPG, two with HVPG > 10 mm Hg, whereas three others had HVPG < 5 mm Hg in spite of having clinical manifestations of portal hypertension.

6 The predominant literature on NRH is in the form of case reports or small case series and there are

only few reports of portal pressure measurements in this condition. In the current issue of the Journal, Bissonnette et al.8 reported hemodynamic measurements, including HVPG, in 21 patients and portal vein pressure gradient (PVPG, portal vein pressure – inferior vena cava pressure) in 12 patients with NRH. The causes of NRH in these patients included oxaliplatin chemotherapy, treatment with purine antagonists, liver transplantation, hematological and rheumatological conditions, and HIV infection. Wnt inhibitor Fifteen out of 21 patients with varices/ascites had HVPG less than 10 mm Hg suggesting a pre-sinusoidal portal hypertension, which was confirmed by a portal vein pressure higher than 12 mm Hg in all 12 patients. Though the majority of patients (15/21) had a pre-sinusoidal component, six patients did have higher HVPG (more

than 10 mm Hg) suggesting sinusoidal portal hypertension.8 These data by Julien et al. thus suggest that both components of portal hypertension (pre-sinusoidal and sinusoidal) occur in patients with NRH. The pre-sinusoidal portal hypertension is related to the well-described vasculopathy (obliterative portal venopathy), while the sinusoidal portal hypertension is probably attributable to sinusoidal obstruction because of compression by regenerative nodules.8 Even though data are sparse, AUY-922 datasheet other studies in patients with NRH have also suggested a mixed type of portal hypertension (pre-sinusoidal and sinusoidal).

see more In one of the case reports, a 47-year-old woman with NRH who underwent HVPG before and after splenectomy had a marked difference between WHVP and FHVP with little difference between portal venous pressure and WHVP; these findings indicated that portal hypertension in NRH was primarily sinusoidal.9 Similar data were shown by two other studies, one another single case report and the other a series of 13 cases.4,10 On the other hand, in a relatively large number of biopsy-proven cases of NRH (n = 14), Arvanitaki and Adler5 suggested that portal hypertension in patients with NRH was pre-sinusoidal. The clinical manifestations included splenomegaly, esophageal varices and variceal bleeding.5 In another recent study, 26 patients receiving 6-thioguanine for inflammatory bowel disease were evaluated with HVPG and liver biopsy.11 Six out of 24 patients (25%) with adequate liver tissue on histology had evidence of NRH. Of six patients with NRH, three had elevated (> 5 mm Hg) HVPG, two with HVPG > 10 mm Hg, whereas three others had HVPG < 5 mm Hg in spite of having clinical manifestations of portal hypertension.

In fact, our experiments using HepaRG cells clearly demonstrated that bezafibrate induced CYP3A4 mRNA expression and activity (Fig. 4A) and inhibited the expression of CYP7A1 mRNA (Fig. 5C) in a dose-dependent manner. Significant up-regulation of CYP3A4 was caused by at

least 10 μM Selleck Mitomycin C of bezafibrate, whereas the serum peak concentration (Cmax) values after oral administration of 400 mg bezafibrate were 9.1-22.7 μM.38 Because the expression of CYP3A4 is mainly controlled by PXR,39 it was strongly suggested that bezafibrate was a ligand of this nuclear receptor, and this hypothesis was proved by the reporter gene assay (Fig. 4B). In addition to PPARα, PXR also regulates hepatic enzyme and transporter activities to exert protective effects against cholestasis. First, the induced CYP3A4 detoxifies xenobiotics and endogenous substances, including the toxic bile acid LCA.40, 41 The C-6α or C-6β position of LCA is hydroxylated by CYP3A4 and nontoxic hyodeoxycholic acid (6α-OH) or murideoxycholic acid (6β-OH) is formed. Second, the activation of PXR up-regulates MDR142 and MRP2,43 which was also observed in our HepaRG cells treated with rifampicin and bezafibrate (Fig. 5B). MDR1 transports

various toxic metabolites and xenobiotics, whereas MRP2 transports organic anions from hepatocytes to bile canaliculi. 3-MA mouse These results further suggest that the down-regulation of CYP7A1 by bezafibrate is caused not only by the activation of PPARα but also by the activation of PXR. Li and Chiang44 demonstrated that hepatocyte nuclear factor 4α (HNF4α; NR2A1) interacts with several coactivators including PGC1α, and that the complex activates the transcription of CYP7A1 in the absence of ligands.45 Ligands for PXR activate PXR to promote its interaction with HNF4α, which disrupts the interaction between HNF4α and PGC1α and results in suppression of CYP7A1 expression. Rifampicin is a more potent ligand of human PXR than bezafibrate (Fig. 4), and has also been shown to have anticholestatic effects in PBC patients.46 However, continuous administration of rifampicin can sometimes result in severe hepatitis.47 In addition to

find more rifampicin and bezafibrate, budesonide, but not prednisolone, is also an agonist of the human PXR.48 Therefore, the therapeutic effects of budesonide on PBC patients may be caused at least in part by the anticholestatic effects by way of the activation of PXR. Hypercholesterolemia and hypertriglyceridemia are often observed in PBC patients. Although it remains controversial whether or not the lipid abnormalities in this disease increase atherosclerotic risk,49 the administration of bezafibrate significantly reduced the serum concentrations of LDL cholesterol and triglycerides. The mechanism of the cholesterol-lowering effect of bezafibrate has not yet been completely elucidated, and at the very least, it is not likely due to a direct inhibition of HMGCR50 (Fig. 5C).

0165), being significantly (10%) lower during Sedation/Entangled than in the Disentangled phase (Z  =  −2.7230, P = 0.0065; Fig. 8). There was no significant difference between ODBA in dive descents between Disentangled and Recovery phases (Z  =  −1.2603, P = 0.2076). During ascents, ODBA did not differ significantly between phases (χ2 = 2.8613, P = 0.2392; Fig. 8). Mean drag forces (N) of gear removed from Eg 3911 were consistently though not significantly

greater at all speeds with buoys attached (Table 4). Sinkline drag forces were intermediate between gear-only and gear-and-buoy configurations (Table 4). Mean drag forces showed no significant difference between surface and 2 m anchor points for gear-only (P = 0.4595), gear-and-buoys (P = 0.4888) or sinkline (P = 0.4965) configurations (Devore 2008). The mean theoretical drag coefficient of a nonentangled right whale (Cd,n) of Eg 3911′s dimensions, swimming at 0.75–2.9 m/s ranged from FK228 concentration 3.7 × 10−3 to 2.9 × 10−3, respectively (mean ± SD; Cd,n = 3.2 × 10−3 ± 0.0003; Fig. 9). The

drag coefficient for each entangled gear scenario was calculated by applying Equation (6) (Cd = DT/(1/2)ρU2Awγkg). Though drag coefficients for Eg 3911 entangled in all gear configurations differed based on the value of k (Fig. 10), the most conservative estimates with k = 3 (Cd,e,go = 3.4 × 10−3 ± 0.0003, Cd,e,gb = 3.7 × 10−3 ± 0.0003, Cd,e,sl = 3.8 × 10−3 ± 0.0004) were significantly greater than in the nonentangled case (Wilcoxon signed rank, P = 0.0156, 0.0312, 0.0078, respectively). Having DAPT made low (Kleiber) and high (3 ×  Kleiber) estimates selleck chemicals of BMR, and using two values of k (1 and 3), we present drag and power requirements as the lower (k = 1, BMR = Kleiber) and upper (k = 3, BMR = 3 ×  Kleiber) bounds of the model results. Drag forces on Eg 3911 while not entangled ranged from 37.2 N to 1,263 N at 0.75–2.9 m/s. The associated total power requirements in the nonentangled condition (Eq. 11) ranged from 2,791 W to 16,140 W (Fig 10). Locomotory power requirements ranged from 191 W to 25,021 W. Drag forces on Eg 3911 entangled in various gear configurations are summarized

in Table 5. Across all gear configurations, mean entangled drag values ranged from 62.1 N to 2,421 N. Increases in total power input over the normal (nonentangled) condition ranged from 4.1% to 58.8% for the gear-only configuration, 4.9% to 82.5% for the sinkline configuration, and 4.8% to 120.9% for the gear-and-buoy configuration (Fig. 9). Locomotory power requirements increased on average 70.5% (SD 9.5) for the gear-only configuration, 91.0% (22.5) for the sinkline configuration, and 101.9% (31.9) for the gear-and-buoy configuration (total range 60.0%–164.6%). Alternatively, to maintain the same power output over the range of swimming speeds, an individual entangled in gear-only, sinkline, and gear-and-buoy configurations would need to decrease swimming speed by 16.2% (SD 1.5), 19.2% (3.0), or 20.5% (3.9), respectively (total range 14.5%–27.7%).

0165), being significantly (10%) lower during Sedation/Entangled than in the Disentangled phase (Z  =  −2.7230, P = 0.0065; Fig. 8). There was no significant difference between ODBA in dive descents between Disentangled and Recovery phases (Z  =  −1.2603, P = 0.2076). During ascents, ODBA did not differ significantly between phases (χ2 = 2.8613, P = 0.2392; Fig. 8). Mean drag forces (N) of gear removed from Eg 3911 were consistently though not significantly

greater at all speeds with buoys attached (Table 4). Sinkline drag forces were intermediate between gear-only and gear-and-buoy configurations (Table 4). Mean drag forces showed no significant difference between surface and 2 m anchor points for gear-only (P = 0.4595), gear-and-buoys (P = 0.4888) or sinkline (P = 0.4965) configurations (Devore 2008). The mean theoretical drag coefficient of a nonentangled right whale (Cd,n) of Eg 3911′s dimensions, swimming at 0.75–2.9 m/s ranged from MG-132 manufacturer 3.7 × 10−3 to 2.9 × 10−3, respectively (mean ± SD; Cd,n = 3.2 × 10−3 ± 0.0003; Fig. 9). The

drag coefficient for each entangled gear scenario was calculated by applying Equation (6) (Cd = DT/(1/2)ρU2Awγkg). Though drag coefficients for Eg 3911 entangled in all gear configurations differed based on the value of k (Fig. 10), the most conservative estimates with k = 3 (Cd,e,go = 3.4 × 10−3 ± 0.0003, Cd,e,gb = 3.7 × 10−3 ± 0.0003, Cd,e,sl = 3.8 × 10−3 ± 0.0004) were significantly greater than in the nonentangled case (Wilcoxon signed rank, P = 0.0156, 0.0312, 0.0078, respectively). Having http://www.selleckchem.com/products/midostaurin-pkc412.html made low (Kleiber) and high (3 ×  Kleiber) estimates selleck compound of BMR, and using two values of k (1 and 3), we present drag and power requirements as the lower (k = 1, BMR = Kleiber) and upper (k = 3, BMR = 3 ×  Kleiber) bounds of the model results. Drag forces on Eg 3911 while not entangled ranged from 37.2 N to 1,263 N at 0.75–2.9 m/s. The associated total power requirements in the nonentangled condition (Eq. 11) ranged from 2,791 W to 16,140 W (Fig 10). Locomotory power requirements ranged from 191 W to 25,021 W. Drag forces on Eg 3911 entangled in various gear configurations are summarized

in Table 5. Across all gear configurations, mean entangled drag values ranged from 62.1 N to 2,421 N. Increases in total power input over the normal (nonentangled) condition ranged from 4.1% to 58.8% for the gear-only configuration, 4.9% to 82.5% for the sinkline configuration, and 4.8% to 120.9% for the gear-and-buoy configuration (Fig. 9). Locomotory power requirements increased on average 70.5% (SD 9.5) for the gear-only configuration, 91.0% (22.5) for the sinkline configuration, and 101.9% (31.9) for the gear-and-buoy configuration (total range 60.0%–164.6%). Alternatively, to maintain the same power output over the range of swimming speeds, an individual entangled in gear-only, sinkline, and gear-and-buoy configurations would need to decrease swimming speed by 16.2% (SD 1.5), 19.2% (3.0), or 20.5% (3.9), respectively (total range 14.5%–27.7%).