Mercury Contamination of an Introduced Generalist Fish of Intermediate Trophic Level.

Mercury contamination is a global issue because mercury concentrations in aquatic systems are influenced by both natural and anthropogenic pathways. Here, liver and muscle total mercury (THg) concentrations in black crappie Pomoxis nigromaculatus from three boreal lakes in southeastern Manitoba, Canada, were related to age, morphology and physiological traits to better understand the dynamics of mercury accumulation in an introduced generalist fish species. These THg concentrations were then compared to black crappie mercury concentrations in other Canadian water bodies and to mercury concentrations in other freshwater fishes in southeastern Manitoba. Age and size had strong positive correlations (P < 0.001, r ≥ 0.60) with muscle mercury concentrations. No evidence of acute point source contamination or physiological impairment in black crappie was found in the study area. Analysis of liver THg revealed the possible impacts of seasonal and ontogenetic differences in diet on exposure. Furthermore, THg analysis of liver and muscle tissue showed how generalist foraging may curb the progressively greater mercury exposure and resultant physiological consequences expected from ontogenetic diet shifts in black crappie. Although there appeared to be temporally varied levels of mercury exposure (i.e., liver THg) by sex, there was no sex effect observed in long-term mercury accumulation in the muscle. Black crappie bioaccumulated less mercury at age than primary piscivore species in the region. These results will help foster a better understanding of mercury biomagnification within a region impacted by legacy mercury.

Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for Pseudomonas aeruginosa survival.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infections and tissue damage. CF macrophages exhibit reduced bacterial killing and increased inflammatory signaling. Iron is elevated in the CF lung and is a critical nutrient for bacteria, including the common CF pathogen Pseudomonas aeruginosa (Pa). While macrophages are a key regulatory component of extracellular iron, iron metabolism has yet to be characterized in human CF macrophages. Secreted and total protein levels were analyzed in non-CF and F508del/F508del CF monocyte derived macrophages (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor. CF macrophage transferrin receptor 1 (TfR1) was reduced with ivacaftor/lumacaftor treatment. When activated with LPS, CF macrophage expressed reduced ferroportin (Fpn). After the addition of exogenous iron, total iron was elevated in conditioned media from CF MDMs and reduced in conditioned media from ivacaftor/lumacaftor treated CF MDMs. Pa biofilm formation and viability were elevated in conditioned media from CF MDMs and biofilm formation was reduced in the presence of conditioned media from ivacaftor/lumacaftor treated CF MDMs. Defects in iron metabolism observed in this study may inform host-pathogen interactions between CF macrophages and Pa.

Physical and economic comparison of pasture-based automatic and conventional milking systems.

Automatic milking systems (AMS) have the potential to increase dairy farm productivity and profitability; however, adoption rates, particularly in pasture-based systems, have been lower than expected. The objectives of this study were to compare the physical and economic performance of pasture-based AMS with conventional milking systems (CMS) and to identify gaps for improving AMS productivity and profitability. We used data from 14 AMS and 100 CMS located in the main Australian dairy regions and collected over 3 yr (2015-2016, 2016-2017, 2017-2018). Farms within similar regions and herd sizes were compared. Results showed that all the main physical performance indicators evaluated such as milk production per cow, milk production per hectare, pasture grazed per hectare, or milk solids per full-time equivalent were similar between systems. The AMS farms had higher overhead costs such as depreciation and repairs and maintenance; however, no differences in total labor costs were observed between systems. Profitability, measured as earnings before interest and tax, operating profit margin, and return on total assets, was not significantly different between AMS and CMS. Opportunities for improving pasture utilization, labor efficiency, and robot utilization in AMS farms were identified. Improving efficiency in these areas could improve productivity and profitability of these systems, and therefore increase the interest of this technology.

Reduced peripheral activity leading to hepato-preferential action of basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes.

AIMS: Basal insulin peglispro (BIL), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine (GL) on endogenous glucose production (EGP), glucose disposal rate (GDR) and lipolysis in patients with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, open-label, four-period, crossover study. Patients received intravenous infusions of BIL and GL, each at two dose levels selected for partial and maximal suppression of EGP, during an 8 to 10 h euglycemic clamp procedure with d-[3-3 H] glucose. RESULTS: Following correction for equivalent human insulin concentrations (EHIC), low-dose GL infusion resulted in similar EGP at the end of the clamp compared to low-dose BIL infusion (GL/BIL ratio of 1.03) but a higher GDR (GL/BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL. Consistent with this, the EHIC-corrected GDR/EGP at the end of the clamp was 1.72-fold greater for GL than BIL following low-dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp. CONCLUSIONS: Compared with GL, BIL restored the hepato-peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.

A surprisingly complex aqueous chemistry of the simplest amino acid. A pulse radiolysis and theoretical study on H/D kinetic isotope effects in the reaction of glycine anions with hydroxyl radicals.

A pulse radiolysis study was carried out of the reaction rate constants and kinetic isotope effects of hydroxyl-radical-induced H/D abstraction from the most-simple alpha-amino acid glycine in its anionic form in water. The rate constants and yields of three predominantly formed radical products, glycyl (NH2-*CH-CO2-), aminomethyl (NH2-*CH2), and aminyl (*NH-CH2-CO2-) radicals, as well as of their partially or fully deuterated analogs, were found to be of comparable magnitude. The primary, secondary, and primary/secondary H/D kinetic isotope effects on the rate constants were determined with respect to each of the three radicals. The unusual variety of products for such an elementary reaction between two small and simple species indicates a complex mechanism with several reactions taking place simultaneously. Thus, a theoretical modeling of the reaction mechanism and kinetics in the gas- and aqueous phase was performed by using the unrestricted density functional theory with the BB1K functional (employing the polarizable continuum model for the aqueous phase), unrestricted coupled cluster UCCSD(T) method, and improved canonical variational theory. Several hydrogen-bonded prereaction complexes and transition states were detected. In particular, the calculations pointed to a significant mechanistic role of the three-electron two-orbital (sigma/sigma* N therefore O) hemibonded prereaction complexes in the aqueous phase. A good agreement with the experimental rate constants and kinetic isotope effects was achieved by downshifting the calculated reaction barriers by 3 kcal mol(-1) and damping the NH(D) stretching frequency by a factor of 0.86.

MCP-1 is highly expressed in peritoneum following midline laparotomy with peritoneal abrasion in a murine model.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is a potent attractant of monocytes both in vitro and in vivo. However, its role in the repair of peritoneal injury is not well established. This study characterizes MCP-1 expression in surgical wounds following peritoneal abrasion in a murine model. METHODS: Twenty-five C57 BL6 female mice underwent a 2-cm midline laparotomy with mechanical abrasion of the right peritoneal wall. The mice were sacrificed at various times ranging from 0 to 7 days. Hemotoxylin and eosin stained sections and tissue extracts were made using peritoneal samples from abraded and unabraded areas in each mouse. An enzyme-linked immunosorbent assay was performed on the specimens to quantitate MCP-1 expression. Values were compared using a t-test. RESULTS: At baseline, there was minimal expression of MCP-1 (<5 pg/mg protein). Following surgery, MCP-1 levels at abraded sites were significantly higher than those at both baseline and unabraded sites at all times up to a week following surgery. Histologic evaluation revealed peritoneal thickening and leukocytic infiltration of only abraded surfaces. CONCLUSION: MCP-1 is highly expressed in peritoneum following laparotomy with peritoneal abrasion. Elevations in MCP-1 levels are identified within 6 h of surgery and persist for up to 1 week. The histologic differences between abraded and unabraded areas may be attributable to differences in MCP-1 expression. Further studies using recombinant MCP-1 and anti-MCP-1 antibody may elucidate this relationship.

Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin preparation.

BACKGROUND: Many patients with diabetes use mixtures of fast-acting (regular human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin to control their blood glucose levels. Premixed insulin is available in a 70%/30% mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients, however, a premixed formulation containing > or =30% regular human insulin can provide too much fast-acting insulin, potentially causing an increased risk for hypoglycemia in the early hours after injection. OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and 15% regular human insulin (85/15) were compared with those of a premixed 70%/30% NPH/regular human insulin preparation and 100% NPH insulin. METHODS: A 12-hour euglycemic clamp approach was used to assess glucose-lowering effects and serum insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg), randomized, double-blind, 3-period, crossover study. RESULTS: From 0 to 8 hours after injection, the glucose-lowering effects and serum insulin levels for the 85/15 premixed insulin preparation were significantly greater than those for NPH insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax) was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak insulin levels did not differ significantly for the 3 preparations, but maximum serum insulin concentration (Cmax(ins)) was significantly different between the groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH: 35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ significantly among preparations during the interval from 8 to 12 hours after injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each preparation during the 12-hour period after injection. CONCLUSIONS: The 85/15 premixed insulin preparation demonstrated clinical pharmacokinetic and pharmacodynamic properties that were intermediate between, and significantly different from, those of NPH insulin and the 70/30 premixed insulin preparation.

The competitive and predatory impacts of the nonindigenous crab Carcinus maenas (L.) on early benthic phase Dungeness crab Cancer magister Dana.

We evaluate the potential competitive and predatory impacts of nonindigenous European green crab Carcinus maenas on native Dungeness crab Cancer magister in the northeast Pacific. The coastal estuaries of Washington State, USA, provide appropriate habitat for recently introduced green crab, yet these areas are important nursery grounds for Dungeness crab and contribute greatly to the coastal crab fishery. Juvenile Dungeness crabs are dependent on limited intertidal epibenthic shell for refuge habitat during early benthic life and experience increased mortality on open sand and mud as a result of predation by fish and birds. Early juveniles throughout the subtidal are similarly at risk due to predation by fish and especially adult conspecifics. Laboratory experiments and infrared video observations revealed that juvenile green crab displace Dungeness crab of equal size from shelters during one-on-one competition. Green crab also consistently win nocturnal foraging trials in which the species compete for fresh, damaged clams. Field and laboratory enclosure experiments show that juvenile Dungeness crab emigrate from oyster shell habitat as a result of competition and predation by adult green crab. Depending on the extent to which the two species overlap, interactions with the dominant nonindigenous species could have a negative influence on juvenile Dungeness crab survival and could conceivably impact recruitment to the fishery. However, current evidence indicates that the distribution of green crab in Washington State is far removed from nursery areas of Dungeness crab.

Effects of structure on alpha C-H bond enthalpies of amino acid residues: relevance to H transfers in enzyme mechanisms and in protein oxidation.

The bond dissociation enthalpies (BDE) of all of the amino acid residues, modeled by HC(O)NHCH(R)C(O)NH(2) (PH(res)), were determined at the B3LYP/6-31G//B3LYP/6-31G level, coupled with isodesmic reactions. The results for neutral side chains with phi, psi angles approximately 180 degrees, approximately 180 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-)(1), are Asn 326; cystine 330; Asp 332; Gln 334; Trp 337; Arg 340; Lys 340; Met 343; His 344; Phe 344; Tyr 344; Leu 344; Ala 345; Cys 346; Ser 349; Gly 350; Ile 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calculated at the ROMP2/6-31G//B3LYP/6-31G level exhibit the same trends but are approximately 7 kJ mol(-)(1) higher. All BDEs are smaller than those of typical secondary or tertiary C-H bonds due to the phenomenon of captodative stabilization. The stabilization is reduced by changes in the phi,psi angles. As a result the BDEs increase by about 10 kJ mol(-)(1) in beta-sheet and 40 kJ mol(-)(1) in alpha-helical environments, respectively. In effect the alpha C-H BDEs can be "tuned" from about 345 to 400 kJ mol(-)(1) by adjusting the local environment. Some very significant effects of this are seen in the current literature on H-transfer processes in enzyme mechanisms and in oxidative damage to proteins. These observations are discussed in terms of the findings of the present study.

Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon.

Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide (LPS)-induced chemoattractant cytokine gene expression: levels of IP-10 mRNA were markedly suppressed in IL-10-treated mouse peritoneal macrophages, whereas the expression of the RANTES mRNA was only modestly reduced. IL-10 inhibited IP-10 mRNA accumulation by reducing IP-10 gene transcription as demonstrated by nuclear run-on analysis. Interestingly, the ability of IL-10 to inhibit expression of IP-10 was dependent on the inducing stimulus; IL-10 did not suppress interferon gamma (IFNgamma)- or IFNbeta-stimulated IP-10 transcription or mRNA accumulation. These results suggested that IL-10 might act indirectly to suppress IP-10 expression by inhibiting LPS-induced class I IFN production. This hypothesis was supported by the following observations. First, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide. Second, IL-10 inhibited the production of IFN/beta-mediated antiviral activity. Finally, the IL-10-mediated suppression of LPS-stimulated IP-10 production could be rescued by cotreatment with IFNbeta.

Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion.

Impaired suppression of plasma nonesterified fatty acids (NEFAs) after glucose ingestion may contribute to glucose intolerance, but the mechanisms are unclear. Evidence that insulin inhibits hepatic glucose output (HGO), in part by suppressing plasma NEFA levels, suggests that impaired suppression of plasma NEFA after glucose ingestion would impair HGO suppression and increase the systemic delivery of glucose. To test this hypothesis, we studied glucose kinetics (constant intravenous [3-3H]glucose [0.4 microCi/min], oral [1-14C]glucose [100 microCi]), whole-body substrate oxidation, and leg glucose uptake in eight normal subjects (age, 39 +/- 9 years [mean +/- SD]; BMI, 24 +/- 2 kg/m2) in response to 75 g oral glucose on two occasions. In one study, plasma NEFAs were prevented from falling by infusion of 20% Liposyn (45 ml/h) and heparin (750 U/h). Plasma glucose rose more rapidly during lipid infusion (P < 0.05), and mean levels tended to be higher after 120 min (6.45 +/- 0.41 vs. 5.81 +/- 0.25 SE, 0.1 < P < 0.05, NS); peak glucose levels were similar. Total glucose appearance (Ra) was higher during lipid infusion due to a higher HGO (28.4 +/- 1.0 vs. 21.2 +/- 1.5 g over 4 h, P < 0.005). Total glucose disposal (Rd) was also higher (88 +/- 2 vs. 81 +/- 3 g in 4 h, P < 0.05). Plasma insulin rose more rapidly after glucose ingestion with lipid infusion, and leg glucose uptake was 33% higher (P < 0.05) during the 1st hour. During lipid infusion, subjects oxidized less glucose (47 +/- 3 vs. 55 +/- 2 g, P < 0.05) and more fat (7.1 +/- 0.8 vs. 3.9 +/- 0.9 g, P < 0.02). In summary, 1) impaired suppression of NEFAs after oral glucose impairs insulin's ability to suppress HGO, and 2) in normal subjects the greater insulin response compensates for the increased systemic glucose delivery by increasing peripheral glucose Rd.

Clinical pathway management of total knee arthroplasty.

Using a retrospective cohort study design, the authors examined complications, readmissions, morbidity and mortality, and function scores in two groups of patients attended by the same surgeon for the year before and the year after the implementation of an outcomes management program with clinical pathways for patients undergoing total knee arthroplasty at an academic health center. The effectiveness of the pathway constantly was adjusted using variance analysis and continuous quality improvement techniques. This program reduced the length of stay by 57% from a premanagement value of 10.9 +/- 5.4 days in 1994 (Group 1) to 4.7 +/- 1.4 days in 1996 (Group 2). Hospital costs (based on an inflation adjusted cost to charge ratio) for all total knees were reduced 11% from $13,328 +/- $3905 in 1994 to $11,862 +/- $4763 in 1996. Preoperative and postoperative knee scores were 41.1 +/- 16.3 and 84.2 +/- 16.0 for Group 1 and 42.5 +/- 13.0 and 87.0 +/- 10.4 for Group 2, respectively. There was no statistically significant difference between the preoperative or the postoperative knee scores of Groups 1 and 2. The application of clinical pathways, variance analysis, and continuous quality improvement toward the treatment of patients who had total knee arthroplasty at an academic health center resulted in significant savings in length of stay without adversely affecting overall outcome.

Structure of the Female Reproductive Tract in the Dungeness Crab (Cancer magister) and Implications for the Mating System.

Anatomical and behavioral aspects of reproduction in female Dungeness crab, Cancer magister, were investigated. Female crabs were collected over a two-year period and external indicators of reproductive condition were recorded. A subset of crabs was retained for macroscopic and histological examination of the reproductive tract. In addition, males and females were held in the laboratory for mating observations, thus providing females of known mating history for dissection. The spermatheca is of the "ventral type," i.e., the vagina and the oviduct open into the spermatheca in close proximity to each other. A novel organ that often contains sperm, the bursa, is separate and distinct from the spermatheca in both position and origin and is reported for the first time for a brachyuran crab. The bursa is located just inside the vulva, distal to the spermatheca, and opens into the vagina. The sperm plug of C. magister, described here for the first time, is unique in form among cancrids. The sperm plug is placed in the vagina by the first male to mate with a soft-shelled female and prevents subsequent access to the spermatheca. However, the sperm plug does not occlude the vulva nor prevent subsequent copulation; ejaculates from subsequent matings are deposited in the bursa. Hypotheses of the possible function of the bursa are discussed.

Primary meningeal tumors in children: correlation of clinical and CT findings with histologic type and prognosis.

PURPOSE: To identify the radiologic features that might help in preoperative differentiation of the meningiomas from the remaining primary meningeal tumors, in particular the malignant tumors. METHODS: The clinical and computed tomographic features of 21 children with histologically proved primary meningeal tumors were analyzed. FINDINGS: Benign tumors (meningiomas) are more likely to occur in older children, to have longer symptom duration, and to have CT appearances similar to the "typical" adult meningioma. Atypical CT features suggest a malignant meningeal tumor, such as meningeal sarcoma, melanoma, or meningeal primitive neuroectodermal tumor. The recent identification of a new subtype of meningioma (a "sclerosing" group) is discussed. This is common in children and the CT and clinical features are similar to those seen in other meningiomas. It is frequently mistaken histologically for an intraaxial tumor, or for an atypical or malignant meningioma. These sclerosing meningiomas may also show brain invasion but despite this, in the short term, the prognosis is no different from other meningiomas. CONCLUSION: The bad reputation previously ascribed to childhood primary meningeal tumors should be confined to that small group that are malignant. Meningiomas have a more favorable outlook.

Oxidized LDL ceroid, and prostaglandin metabolism in human atherosclerosis.

A noted histological feature of human atherosclerotic lesions upon dissection is the presence of a 'pigment' referred to as ceroid; however the significance of ceroid in human fatty streaks and atherosclerotic plaques is not certain. The research focus to this point has presumed that ceroid synthesis and intracellular accumulation is harmful and may have adverse effects on lesion progression or reversibility. Alternatively, ceroid production may be a defense mechanism employed by cells in the artery wall to prevent uncontrolled synthesis and release of prostaglandins (PGs) or prostaglandin-precursors locally. Export of PGs or PG precursors may promote blood platelet aggregation at the site of export. A feedback inhibition mechanism will arrest the cellular export of prostaglandins, thus ending a potentially disastrous premature clotting event.

Investigation of complications of paranasal sinusitis in children - abstract

The on-going study in patients requiring hospitalization for paranasal sinusitis investigates the extent and spread of the infection on admission. Children with paranasal sinusitis are admitted to hospital if they develop fever, proptosis, ophthal moplegia, eyelids swollen shunt, or decrease in consciousness level. They undergo CT scanning on admission, to determine the involvement of other craniofacial compartments. Complications of paranasal sinusitis arise with breach of the sinus walls and spread to the orbit or intracranial space. Orbital sinusitis or abscess formation may follow, while intracraniallym empyema and brain abscess may arise. These complications are readily recognised by CT examination. The use of computerised tomography in the early investigation of spread of paranasal sinusitis affords effective decision-making for appropriate medical and surgical management of this potentially dangerous infection (AU)

AIDS-related vacuolar myelopathy is not associated with coinfection by human T-lymphotropic virus type I.

Assessment of antibodies against human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunoassay, immunofluorescence, and Western blot was undertaken in patients with pathologically or clinically diagnosed acquired immunodeficiency syndrome-related vacuolar myelopathy to determine whether this retrovirus could be etiologically implicated in this disorder. No serological evidence for HTLV-I was found in the patients with vacuolar myelopathy, though 1 patient with an atypical myelopathy did have antibodies against HTLV-I.