Assessment of trace metal contamination in mangrove ecosystems from Senegal, West Africa.

The inorganic contamination of sediment and harvested molluscs was investigated in the mangrove environment of Southern West Senegal. Trace metals were analysed in surface sediments, two bivalves (Arca senilis and Crassostera gasar) and three gastropods (Conus spp., Hexaplex duplex and Pugilina morio) collected from four stations: Dionewar, Niodor and Falia localised in the Saloum Delta, and Fadiouth from the Petite Côte. A geochemical normalisation approach by using aluminium allowed for discrimination of sediment contamination among sites. Indeed, Fadiouth appeared highly contaminated with Cd, Hg and Ni compared to the Saloum Delta. For all mangrove sites, trace metals exhibited significant higher concentrations (on a dry weight basis) in shellfish compared to sediments, excepted for Ni and Pb. The distribution pattern followed a similar global trend in molluscs regardless of the spatio-temporal variability, with the predominance of Zn (80% of total metals) followed by Cu and Cd. However, strong differences of metal bioavailability and bioaccumulation in biota were demonstrated, revealing the requirement of employing a suite of organism bioindicators to monitor metal contamination in mangrove ecosystems. From an ecotoxicological point of view, trace metal levels in sediments from the Petite Côte and the Sine-Saloum Estuary were below the effects range-low (ERL) threshold limit of the sediment quality guidelines for adverse biological effects (SQGs). On the opposite, some concerns about Cd contamination of edible shellfish from Southern West Senegal were highlighted, from both the safety point of view of local populations' health, and the chemical quality point of view of exported resources.

Echocardiography and non-invasive imaging in cardiac resynchronization therapy.

The beneficial effects of cardiac resynchronization therapy (CRT) on morbidity and mortality in advanced heart failure patients have been extensively demonstrated. However, previous single- and multicenter studies demonstrated that approximately 30-40% of CRT patients do not show significant clinical improvement or LV reverse remodeling despite fulfilling current inclusion criteria. In search of novel indices that may help to improve the selection of responders to CRT, non-invasive multimodality imaging has provided further insight into the mechanisms underlying CRT response. LV dyssynchrony, extent and location of myocardial scar and LV lead position have shown to be independent determinants of CRT response. An integrated evaluation of these three pathophysiological mechanisms may provide a more accurate selection of heart failure patients who will benefit from CRT and may maximize the cost-effectiveness of this therapy. The present review article provides a critical appraisal of the role of multimodality imaging in the selection of heart failure patients who are candidates for CRT with special focus on the assessment of LV mechanical dyssynchrony, LV myocardial scar tissue extent and LV lead position.

Intermittent claudication: From its risk factors to its long-term prognosis in men. The Quebec Cardiovascular Study.

BACKGROUND: The natural history of intermittent claudication, from its risk factors to its cardiovascular prognosis, has been reported in few prospective studies. OBJECTIVE: To assess incident intermittent claudication, as well as its risk factors and long-term prognosis in men. METHODS: A random sample of 4376 men 35 to 64 years of age from Quebec City (Quebec), who were free of cardiovascular disease (CVD), was evaluated in 1974 for CVD risk factors and followed until 1998. To assess the prognosis, the event rates between 1985 and 1998 were computed among men with incident claudication without other CVD, incident survivors of a first myocardial infarction (MI) without other CVD and men free of CVD between 1974 and 1985. RESULTS: From 1974 to 1998, 300 men developed intermittent claudication. Tobacco consumption, high systolic blood pressure and diabetes at least doubled the adjusted RR (aRR) of intermittent claudication. In 1985, there were 80 claudicants, 2868 men free of CVD and 68 survivors of a first MI. During the 13-year follow-up, a new CVD occurred in 48.8% of the claudicants, in 18.9% of men without CVD (aRR 2.08; 95% CI 1.48 to 2.90) and in 45.6% of MI survivors (aRR compared with claudicants 1.12; 95% CI 0.69 to 1.79). There was also no significant difference between claudicants and MI survivors for fatal CVD, nonfatal CVD and total mortality. CONCLUSIONS: Men with intermittent claudication are at high risk for CVD that may be equivalent to men with previous MI.

Patient assessment for cardiac resynchronization therapy: Past, present and future of imaging techniques.

It has been proposed that dyssynchrony assessment before cardiac resynchronization therapy (CRT) implantation could help predict response to CRT. It is known that up to 40% of patients who receive a CRT device for established indications do not respond to CRT. Great expectations came from the Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) study, which would finally identify the ultimate echocardiographic dyssynchrony criteria to help select responders. The recently published PROSPECT trial failed to identify an ideal parameter of dyssynchrony. Patient selection for CRT should involve a multimodal approach, and new promising tools are being investigated in that view. The present review integrated new data coming from the exciting field of imaging with currently available evidence to generate a stepwise approach to patient selection.

Size and shape of the resection surface geometry of the osteoarthritic knee in relation to total knee replacement design.

This study examines the resection surface geometry of the femur, tibia, and patella in relation to the design of total knee implants. Using a technique known as principal component analysis (PCA), the variation in the resection geometry of the knee was summarized. Of the total variation of the knee, 58 per cent was due to variation in size and 14 per cent was due to varying femoral intercondylar notch width. A PCA was performed on each bone separately and it was found that 60 per cent, 76 per cent and 71 per cent of variation was due to size for the femur, tibia, and patella respectively. Femoral and tibial size were highly correlated (r = 0.95) while patellar size had poorer correlation with both femoral and tibial size (r < 0.7). Simple linear dimensions (femoral epicondylar width or tibial mediolateral width) were reliable indicators of knee size. The effect of shape variation, which is generally not accounted for in implant design, was measured. The resected surfaces of each subject were compared with a model of the resection surfaces of the knee which varied in size but not shape. The maximum overhang and underhang of the model on the resection surfaces were measured. There was average maximum model overhang of 3.6 mm and underhang of 3.9 mm in the femur, 2.3 mm overhang and 1.9 mm underhang in the tibia, and 2.6 mm overhang and 2.5 mm underhang in the patella. The maximum coverage that an implant can be expected to provide for a population is quantified. Implant designs which include some shape as well as size variation improve on the implant fit.

A genetic test of bioactive gibberellins as regulators of heterosis in maize.

This study tested the hypothesis that gibberellin levels were responsible for the superior growth habit of hybrids (i.e., heterosis). If this were true, plants reduced in their capacity to produce gibberellin, such as maize plants homozygous for dwarf1 (d1), should display a lesser heterotic response. The d1 mutation was introgressed into two inbred lines of maize, B73 and Mo17, for seven generations. Plants segregating for the dwarf phenotype were produced both by self-fertilizing the introgressed inbred lines and by making reciprocal crosses between them to produce hybrids. Measurements were made of several physical traits. The results indicated that the hybrid dwarf plants experienced no loss of heterosis relative to their normal siblings. These results exclude the possibility that modulation of bioactive gibberellins is a major underlying basis of the heterotic response.

Minichromosomes derived from the B chromosome of maize.

Fourteen minichromosomes derived from the B chromosome of maize are described. The centromeric region of the B chromosome contains a specific repetitive DNA element called the B repeat. This sequence was used to determine the transmission frequency of the different types of minichromosomes over several generations via Southern blot analysis at each generation. In general, the minichromosomes have transmission rates below the theoretical 50% frequency of a univalent chromosome. The gross structure of each minichromosome was determined using fluorescence in situ hybridization (FISH) on root tip chromosome spreads. The presence of the B centromeric repeat and of the adjacent heterochromatic knob sequences was determined for each minichromosome. In two cases, the amount of the centromeric knob repeat is increased relative to the progenitor chromosome. Other isolates have reduced or undetectable levels of the knob sequence. Potential uses of the minichromosomes are discussed.

The influence of design, materials and kinematics on the in vitro wear of total knee replacements.

Debris-induced osteolysis due to surface wear of ultra high molecular weight polyethylene (UHMWPE) bearings is a potential long-term failure mechanism of total knee replacements (TKR). This study investigated the effect of prosthesis design, kinematics and bearing material on the wear of UHMWPE bearings using a physiological knee simulator. The use of a curved fixed bearing design with stabilised polyethylene bearings reduced wear in comparison to more flat-on-flat components which were sterilised by gamma irradiation in air. Medium levels of crosslinking further improved the wear resistance of fixed bearing TKR due to resistance to strain softening when subjected to multidirectional motion at the femoral-insert articulating interface. Backside motion was shown to be a contributing factor to the overall rate of UHMWPE wear in fixed bearing components. Wear of fixed bearing prostheses was reduced significantly when anterior-posterior displacement and internal-external rotation kinematics were reduced due to decreased cross shear on the articulating surface and a reduction in AP displacement. Rotating platform mobile bearing prostheses exhibited reduced wear rates in comparison to fixed bearing components in these simulator studies due to redistribution of knee motion to two articulating interfaces with more linear motions at each interface. This was observed in two rotating platform designs with different UHMWPE bearing materials. In knee simulator studies, wear of TKR bearings was dependent on kinematics at the articulating surfaces and the prosthesis design, as well as the type of material.

A test for a metastable epigenetic component of heterosis using haploid induction in maize.

We conducted a test to detect if there is a heritable epigenetic component to hybrid vigor and/or inbreeding depression. The impetus for this work was a classical study of the effect of homozygosis on the expression of the maize red color ( r1) locus. It had been shown that maintaining R1 mottling alleles in the homozygous state over several generations produces a progressive decrease of their paternally imprinted expression. This effect is reversed by R1/r1 allele heterozygosity. If this behavior were characteristic of many regulatory genes, then such a phenomenon could contribute to inbreeding depression and heterosis. To examine this question, inbreds of Mo17 and B73 and the two reciprocally produced hybrids were crossed by Stock 6 to generate four classes of maternal haploids. The mature haploid plants were measured for several quantitative traits. If inbreeding depression results from an accumulating heritable effect that is reversed by the hybrid state, one would expect the haploids derived from the hybrids to perform better than those derived from the inbred lines. The hybrid-derived haploids did not exhibit greater average performance than the inbred-derived haploids. These data fail to support the hypothesis that inbreeding depression and heterosis have a metastable epigenetic component.

Maize tertiary trisomic stocks derived from B-A translocations.

Reciprocal translocations between supernumerary B chromosomes and the basic complement of A chromosomes in maize have resulted in a powerful set of tools to manipulate the dosage of chromosomal segments. From 15 B-A reciprocal translocation stocks that have the B-A chromosome genetically marked we have developed tertiary trisomic stocks. Tertiary trisomics are 2n + 1 aneuploids where the extra chromosome is a translocation element, in this case a B-A chromosome. Whereas B-A translocations produce aneuploidy in the sperm, the tertiary trisomic plant efficiently transmits hyperploid gametes maternally. Because the B-A tertiary trisomic stocks and the B-A translocation stocks from which they were derived are introgressed into the W22 inbred line, the effects of maternally and paternally transmitted trisomic B-A chromosomes can be compared. Data are presented on both the male and female transmission rates of the B-A chromosomes in the tertiary trisomic stocks.

Investigation of wear of knee prostheses in a new displacement/force-controlled simulator.

The performance of two knee simulators designed by ProSim (Manchester, UK) was evaluated by comparison of the wear seen in the press-fit condylar (PFC) Sigma (DePuy) knee prosthesis. Twelve specimens of the same design and manufacturing specification, were subjected to a wear test of 2 x 10(6) cycles duration using bovine serum as a lubricant. The anterior/posterior displacement and internal/external rotation inputs were based on the kinematics of the natural knee. International Standards Organization (ISO) standards were used for the flexion and axial load. The wear rates and wear scar areas were compared across all stations. The mean wear rates found were 17.6+/-5 mm3/10(6) cycles for stations 1 to 6 and 19.6+/-4 mm3/10(6) cycles for stations 7 to 12, resulting in an overall mean wear rate of 18.1+/-3 mm3/10(6) cycles. The differences between the two simulators were not significant. The average wear scar area seen on inserts from stations I to 6 was calculated at 32.4+/-1 per cent of the intended articulating surface. Similarly on stations 7 to 12 the average wear scar area was 30.7+/-3 per cent. The wear scars seen were a good physiological representation of those found from clinical explant data. This study has shown good repeatability from the simulator, both within and between the simulators.

Dosage-dependent gene regulation in multicellular eukaryotes: implications for dosage compensation, aneuploid syndromes, and quantitative traits.

Evidence from a variety of data suggests that regulatory mechanisms in multicellular eukaryotes have evolved in such a manner that the stoichiometric relationship of the components of regulatory complexes affects target gene expression. This type of mechanism sets the level of gene expression and, as a consequence, the phenotypic characteristics. Because many types of regulatory processes exhibit dosage-dependent behavior, they would impact quantitative traits and contribute to their multigenic control in a semidominant fashion. Many dosage-dependent effects would also account for the extensive modulation of gene expression throughout the genome that occurs when chromosomes are added to or subtracted from the karyotype (aneuploidy). Moreover, because the majority of dosage-dependent regulators act negatively, this property can account for the up-regulation of genes in monosomics and hemizygous sex chromosomes to achieve dosage compensation.

Quantification of third body damage to the tibial counterface in mobile bearing knees.

Fourteen pairs of explanted low contact stress (LCS) tibial interface components: six rotating platform (RP), six meniscal (MN) and two anterior-posterior (AP) glide designs, have been analysed with particular attention paid to the condition of the tibial counterfaces. The average surface roughness, Ra, for the tibial trays ranged from 0.01 to 0.087 micron, significantly greater than the unworn control measurement of 0.008 micron. The scratch geometry analysis showed that the scratch peaks were found to be consistently of a lower aspect ratio than the scratch valleys and under 1 micron in height (average asperity height Rp = 0.52 micron, aspect ratio delta p = 0.01, average asperity depth Rv = 1.10 microns, delta v = 0.05). The largest scratches were 3-4 microns in both Rp and Rv. In vitro tests have shown that ultra-high molecular weight polyethylene (UHMWPE) wear increases in the presence of counterface scratches perpendicular to the direction of motion. In these explants, the unidirectional motion produced scratches parallel to the direction of sliding which is predicted to produce a smaller increase in UHMWPE wear. Other designs in mobile bearing knees have less constrained motion at the tibial counterface and this has been shown to accelerate wear; it may also lead to a further increase in wear in the presence of third body scratches. It may be possible in future knee designs to reduce this type of wear damage by introducing alternative materials or coatings which are more resistant to scratching and surface roughening.

Simulation of tibial counterface wear in mobile bearing knees with uncoated and ADLC coated surfaces.

A multidirectional pin-on-plate reciprocating machine was used to compare the wear performance of UHMWPE sliding against cast cobalt chrome (CoCr) plates that were either untreated or coated with Amorphous Diamond Like Carbon (ADLC). The test conditions were based on a 1/5 scale model representative of in vivo motion at the tibial counterfaces of unconstrained mobile bearing knees. The average +/- STERR wear rates were 13.78+/-1.06 mm3/Mcycles for the ADLC counterfaces and 0.504+/-0.12 mm3/Mcycles for the control CoCr counterfaces. All of the pins run on the ADLC counterfaces exhibited the same patterns of blistering along the central axis, and severe abrasion elsewhere to the extent that all of the original machining marks were removed after just one week of testing. The average value of friction coefficient was 0.24 for the ADLC counterfaces and 0.073 for the control CoCr counterfaces. The factor of 3.5 increase was statistically significant at p < 0.05. In the tribological evaluation of ADLC coatings for tibial trays in mobile bearing knees, this study shows that this specific Physical Vapour Deposition (PVD) ADLC showed significantly poorer frictional and wear performance than uncoated surfaces which was sufficient to negate any potential benefits of improved resistance to third body damage.

Nuclear gene dosage effects upon the expression of maize mitochondrial genes.

Each mitochondrion possesses a genome that encodes some of its own components. The nucleus encodes most of the mitochondrial proteins, including the polymerases and factors that regulate the expression of mitochondrial genes. Little is known about the number or location of these nuclear factors. B-A translocations were used to create dosage series for 14 different chromosome arms in maize plants with normal cytoplasm. The presence of one or more regulatory factors on a chromosome arm was indicated when variation of its dosage resulted in the alteration in the amount of a mitochondrial transcript. We used quantitative Northern analysis to assay the transcript levels of three mitochondrially encoded components of the cytochrome c oxidase complex (cox1, cox2, and cox3). Data for a nuclearly encoded component (cox5b) and for two mitochondrial genes that are unrelated to cytochrome c oxidase, ATP synthase alpha-subunit and 18S rRNA, were also determined. Two tissues, embryo and endosperm, were compared and most effects were found to be tissue specific. Significantly, the array of dosage effects upon mitochondrial genes was similar to what had been previously found for nuclear genes. These results support the concept that although mitochondrial genes are prokaryotic in origin, their regulation has been extensively integrated into the eukaryotic cell.

Comparison of wear in a total knee replacement under different kinematic conditions.

A six station ProSim (Manchester, UK) knee simulator was used to assess the wear of six PFC (DePuy) fixed bearing total knee replacements under two different kinematic conditions defined as low and high kinematic inputs. The high kinematics displacement and rotation inputs were based on the kinematics of the natural knee with ISO standards used for the axial load and flexion. Low kinematics were defined as approximately half the magnitude. The six specimens were run for three million cycles under low kinematics and three million cycles under high kinematics. The mean wear rate found during the low kinematics phase was 7.7 +/- 2 mm3 per million cycles. This then increased significantly to an average wear rate of 41 +/- 14 mm3 during the high kinematics input phase. The wear areas were characterized by a predominant damage mode of burnishing with some abrasive wear occurring during the high kinematics phase. This study supports the findings that introduction of cross-shearing of the polyethylene by introducing both rotational and anterior/posterior displacement increases the wear rate. This has implications for younger patients with higher levels of activity that need knee replacements.

Wear of fixed bearing and rotating platform mobile bearing knees subjected to high levels of internal and external tibial rotation.

In order to extend the lifetime of total knee replacements (TKR) in vivo, reduction of the volumetric wear rate of ultra high molecular weight polyethylene (UHMWPE) bearings remains an important goal. The volume of wear debris generated in fixed bearing total knee devices increases significantly when subjected to higher levels of internal-external rotation and anterior-posterior displacement. Six PFC Sigma fixed bearing TKR were compared with six LCS rotating platform mobile bearing knees using a physiological knee simulator with high rotation kinematic inputs. The rotating platform polyethylene inserts exhibited a mean wear rate which was one-third of that of the fixed bearing inserts despite having increased femoral contact areas and additional tibial wear surfaces. The rotating platform design decouples knee motions, by allowing unidirectional motion at the tray-insert articulation, which reduces rotation at the femoral-insert counterface. This translation of complex knee motions into more unidirectional motions results in molecular orientation of the UHMWPE and reduced volumetric wear.

Negative crossover interference in maize translocation heterozygotes.

Negative interference describes a situation where two genetic regions have more double crossovers than would be expected considering the crossover rate of each region. We detected negative crossover interference while attempting to genetically map translocation breakpoints in maize. In an attempt to find precedent examples we determined there was negative interference among previously published translocation breakpoint mapping data in maize. It appears that negative interference was greater when the combined map length of the adjacent regions was smaller. Even positive interference appears to have been reduced when the combined lengths of adjacent regions were below 40 cM. Both phenomena can be explained by a reduction in crossovers near the breakpoints or, more specifically, by a failure of regions near breakpoints to become competent for crossovers. A mathematical explanation is provided.

Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.

OBJECTIVES: To study the effect of cell differentiation on the vulnerability of human neural cell types to human cytomegalovirus (HCMV) infection. STUDY DESIGN/METHODS: Primary cultures of human fetal neuroepithelial stem cells and differentiating neuroepithelial precursor cells were infected with HCMV strain AD169. Infectious virus production, apoptosis, and viral-associated cytopathic effects then were examined over a 5-day period. RESULTS: HCMV established productive infection in these cells, generating 10-fold amplification of infectious virus. There was no significant difference in the percentage of apoptotic cells in HCMV-infected versus mock-infected cultures. HCMV antigen and specific cytopathic effects were observed in differentiating astrocytes and neurons, although HCMV antigen was 2-fold more frequent among postmitotic neurons. CONCLUSIONS: Neuroepithelial precursor cells and differentiating astrocytes and neurons are permissive to cytopathic HCMV infection, suggesting that the fetal human central nervous system is vulnerable to HCMV-induced neuronal injury at its earliest stages of development.

An experimental model of tibial counterface polyethylene wear in mobile bearing knees: the influence of design and kinematics.

Current designs of mobile bearing knees have different kinematics at the tibial counterface articulation; unidirectional represented by linear tracks and rotating platform designs, and multidirectional represented by reduced constraint designs with motion of the tibial surface in A-P and M-L directions simultaneously. One fifth scale experimental models of the tibial counterface articulation have been developed with mean contact stresses of 0.6 MPa. The unidirectional model had a linear reciprocating motion with a 10 mm stroke, the multidirectional model had a reciprocating motion with a 10 mm stroke and simultaneous rotation of +/- 7.5 degrees. Six specimens of GUR415 polyethylene were tested for each model, sliding on polished cobalt chrome counterfaces with Ra < 0.01 micron in 25% bovine serum lubricant. The mean +/- STERR wear rates were: unidirectional 0.045 +/- 0.015 mm3/million cycles and multidirectional 0.44 +/- 0.15 mm3/million cycles. Applying the scaling factor of 5, the predicted wear rates in actual knee prostheses were: unidirectional 0.23 mm3/million cycles and multidirectional 2.2 mm3/million cycles. The order of magnitude increase in wear rate was statistically significant (p = 0.05).