Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel-titanium bone graft substitute

Porous nickel-titanium (NiTi) alloy is a promising new material for a bone graft substitute with good strength properties and an elastic modulus closer to that of bone than any other metallic material. The purpose of this study was to evaluate the effect of porosity on the osteointegration of NiTi implants in rat bone. The porosities (average void volume) and the mean pore size (MPS) were 66.1% and 259+/-30 microm (group 1, n=14), 59.2% and 272+/-17 microm (group 2, n=4) and 46.6% and 505+/-136 microm (group 3, n=15), respectively. The implants were implanted in the distal femoral metaphysis of the rats for 30 weeks. The proportional bone-implant contact was best in group 1 (51%) without a significant difference compared to group 3 (39%). Group 2 had lower contact values (29%) than group 1 (p=0.038). Fibrotic tissue within the porous implant was found more often in group 1 than in group 3 (p=0.021), in which 12 samples out of 15 showed no signs of fibrosis. In conclusion, porosity of 66.1% (MPS 259+/-30 microm) showed best bone contact (51%) of the porosities tested here. However, the porosity of 46.6% (MPS 505+/-136 microm) with bone contact of 39% was not significantly inferior in this respect and showed lower incidence of fibrosis within the porous implant.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.     

A modified human ELISPOT assay to detect specific responses to primary tumor cell targets

Background  

The desired outcome of cancer vaccination is to induce a potent T cell response which can specifically recognize and eliminate autologous tumor cells in vivo. Accordingly, immunological assays that demonstrate recognition of native tumor cells (tumor-specific) may be more clinically relevant than assays that demonstrate recognition of tumor protein or peptide (antigen-specific).     

Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study

OBJECTIVE: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population. METHODS: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology. RESULTS: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials. In line with trial observations, the projected HIV impacts were larger for the ST intervention in Mwanza than for the MT intervention in Rakai or the IEC and IEC + ST interventions in Masaka. All 4 simulated intervention strategies were more effective in reducing incidence of HIV infection in Mwanza than in either Rakai or Masaka. CONCLUSIONS: Population differences in sexual behavior, curable STD rates, and HIV epidemic stage can explain most of the contrast in HIV impact observed between the 3 trials. This study supports the hypothesis that STD management is an effective HIV prevention strategy in populations with a high prevalence of curable STDs, particularly in an early HIV epidemic.     

Aggregation of childhood leukemia in geographic areas of Greece)

A total of 872 children aged up to 14 years, who were diagnosed withleukemia in Greece during the decade 1980-89, were allocated by place ofresidence to the 601 administrative districts of the country. Evaluation ofspatial clustering was done using the Potthoff-Whittinghill method, whichvalidly assesses heterogeneity of leukemia risk among districts with variableexpected numbers of cases. There was highly significant evidence for spatialclustering occurring particularly among children living in urban and, to alesser extent, semi-urban areas. The evidence was stronger for childrenyounger than 10 years old, applied also to children in different five-yearage groups, and persisted when cases of acute lymphoblastic leukemia wereanalyzed separately. These findings provide support to the hypothesis thatlocalized environmental exposures could contribute to the etiology ofchildhood leukemia, but they cannot distinguish between exposures of physicalor chemical nature, nor can they exclude socially conditioned patterns ofexposure to infectious agents.     

The implication of nitric oxide in the process of bacterial translocation

Since there is increasing evidence indicating nitric oxide [NO] would play a role in sepsis, we decided to investigate whether this multifaceted mediator is directly implicated in the process of bacterial translocation. A total of 48 rats received intraperitoneal either Zymosan A (group Z) for systemic inflammation production or sodium chloride solution (controls); they were then further subdivided into three groups of eight animals each, being given, through the tail vein: L-NAME (N-nitro-L-arginine] for inhibition of NO production; SNP (sodium nitroprusside) as NO donor; or sodium chloride as control. After 2 h, the mesenteric lymph node complex was excised, under sterile conditions, and, using standard bacteriological techniques, bacterial translocation was assessed as colony forming units per gram of tissue (CFU/g). Statistical evaluation of the bacteriological data revealed a significant increase of bacterial translocation in all rats subjected to systemic inflammation (group Z) versus controls (P = 0.01) Control rats that were subjected to L-NAME treatment exhibited a statistically significant increase (P = 0.001) in CFU/g compared to sodium chloride treated rats, while SNP treatment revealed no difference in relation to sodium chloride treated rats. Group Z rats, subjected to L-NAME treatment, similarly exhibited a statistically significant increase (P = 0.01) in CFU/g compared to sodium chloride treated rats, while SNP treatment led to a statistical increase of bacterial translocation in relation to sodium chloride treated rats (P = 0.05). The results of this study lead us to suggest that NO appears to participate in the process of bacterial translocation.     

Periods of rest in fMRI contain individual spontaneous events which are related to slowly fluctuating spontaneous activity

fMRI studies of brain activity at rest study slow (<0.1 Hz) intrinsic fluctuations in the blood‐oxygenation‐level‐dependent (BOLD) signal that are observed in a temporal scale of several minutes. The origin of these fluctuations is not clear but has previously been associated with slow changes in rhythmic neuronal activity resulting from changes in cortical excitability or neuronal synchronization. In this work, we show that individual spontaneous BOLD events occur during rest, in addition to slow fluctuations. Individual spontaneous BOLD events were identified by deconvolving the hemodynamic impulse response function for each time point in the fMRI time series, thus requiring no information on timing or a‐priori spatial information of events. The patterns of activation detected were related to the motor, visual, default‐mode, and dorsal attention networks. The correspondence between spontaneous events and slow fluctuations in these networks was assessed using a sliding window, seed‐correlation analysis, where seed regions were selected based on the individual spontaneous event BOLD activity maps. We showed that the correlation varied considerably over time, peaking at the time of spontaneous events in these networks. By regressing spontaneous events out of the fMRI signal, we showed that both the correlation strength and the power in spectral frequencies <0.1 Hz decreased, indicating that spontaneous activation events contribute to low‐frequency fluctuations observed in resting state networks with fMRI. This work provides new insights into the origin of signals detected in fMRI studies of functional connectivity. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.