Magnetic resonance imaging of stem cell apoptosis in arthritic joints with a caspase activatable contrast agent.

About 43 million individuals in the U.S. encounter cartilage injuries due to trauma or osteoarthritis, leading to joint pain and functional disability. Matrix-associated stem cell implants (MASI) represent a promising approach for repair of cartilage defects. However, limited survival of MASI creates a significant bottleneck for successful cartilage regeneration outcomes and functional reconstitution. We report an approach for noninvasive detection of stem cell apoptosis with magnetic resonance imaging (MRI), based on a caspase-3-sensitive nanoaggregation MRI probe (C-SNAM). C-SNAM self-assembles into nanoparticles after hydrolysis by caspase-3, leading to 90% amplification of (1)H MR signal and prolonged in vivo retention. Following intra-articular injection, C-SNAM causes significant MR signal enhancement in apoptotic MASI compared to viable MASI. Our results indicate that C-SNAM functions as an imaging probe for stem cell apoptosis in MASI. This concept could be applied to a broad range of cell transplants and target sites.

Determination of the oxide layer thickness in core-shell zerovalent iron nanoparticles.

Zerovalent iron (nZVI) nanoparticles have long been used in the electronic and chemical industries due to their magnetic and catalytic properties. Increasingly, applications of nZVI have also been reported in environmental engineering because of their ability to degrade a wide variety of toxic pollutants in soil and water. It is generally assumed that nZVI has a core-shell morphology with zerovalent iron as the core and iron oxide/hydroxide in the shell. This study presents a detailed characterization of the nZVI shell thickness using three independent methods. High-resolution transmission electron microscopy analysis provides direct evidence of the core-shell structure and indicates that the shell thickness of fresh nZVI was predominantly in the range of 2-4 nm. The shell thickness was also determined from high-resolution X-ray photoelectron spectroscopy (HR-XPS) analysis through comparison of the relative integrated intensities of metallic and oxidized iron with a geometric correction applied to account for the curved overlayer. The XPS analysis yielded an average shell thickness in the range of 2.3-2.8 nm. Finally, complete oxidation reaction of the nZVI particles by Cu(II) was used as an indication of the zerovalent iron content of the particles, and these observations further correlate the chemical reactivity of the particles and their shell thicknesses. The three methods yielded remarkably similar results, providing a reliable determination of the shell thickness, which fills an essential gap in our knowledge about the nZVI structure. The methods presented in this work can also be applied to the study of the aging process of nZVI and may also prove useful for the measurement and characterization of other metallic nanoparticles.

Exercise interventions for smokers with a history of alcoholism: exercise adherence rates and effect of depression on adherence.

This study examined the adherence rates and the effect of depression on adherence in two studies conducted among smokers with a past history of alcoholism. In both studies, subjects participated in a 12-session group-based exercise intervention for smoking cessation. The target quit date (TQD) was Session 8. Participants in Study 1 were 73 smokers (43% female). Exercise instructions began at Session 8 and continued through Session 12. Mean frequency and number of minutes of exercise decreased during the 4 weeks of exercise treatment (P<.001). Study 2, conducted with 18 smokers (50% female), examined the feasibility of commencing exercise at Session 1, well before the TQD. The mean number of minutes exercised increased from Sessions 1 to 12 (P=.013). In both studies, average session attendance was high (82%). Combining subjects from both studies, depressed smokers at baseline reported greater mean frequency of exercise per week than nondepressed smokers (P=.05). The results suggest that depressed smokers can be engaged in an exercise program. Further research is needed to determine if commencing exercise early during treatment, prior to the TQD, improves adherence.

Utility and accuracy of collateral reports of smoking status among 256 abstinent alcoholic smokers treated for smoking cessation.

This study examined the utility and accuracy of collateral reports of smoking status among 256 abstinent alcoholic smokers (140 males, 116 females) treated for smoking cessation. Data were gathered prospectively from two randomized clinical trials of behavioral smoking cessation treatment conducted in San Diego, CA. The mean age of the participants was 42.0 years (S.D.= 10.0) and 93% were Caucasian. Self-reported smoking status was obtained at posttreatment (1 week after the target quit date) and at 1 year. Collateral reports obtained by telephone and expired air carbon monoxide (CO) levels of < 10 ppm were used to confirm self-reported smoking status. Collateral reports were available for 89.1% of subjects at posttreatment and 90.6% of subjects at 1 year. The smoking abstinence rates were similar when using collateral reports or CO confirmation of smoking status at both time points. Collateral reports refuted self-reported abstinence as often or more than CO levels, and showed relatively high concordance with CO levels. In conclusion, collateral reports have utility and are reasonably accurate for confirming self-reported smoking status in clinical trials of smoking cessation for abstinent alcoholic smokers.

Effect of depressive symptoms on smoking abstinence and treatment adherence among smokers with a history of alcohol dependence.

This study examined the effect of depressive symptoms on smoking abstinence and treatment adherence among smokers with a past history of alcohol dependence. Participants (24 women, 27 men) were randomly assigned to behavioral counseling (BC) or behavioral counseling plus cognitive-behavioral mood management training (CBT). The Hamilton Rating Scale for Depression (HRSD; M. Hamilton, 1967) was administered to assess baseline depressive symptoms. Participants who received CBT and had higher HRSD scores were more likely to achieve short-term abstinence from smoking and attend more treatment sessions than those with lower depression scores, whereas for BC participants the effect of HRSD scores was the opposite. Smokers with a history of alcohol dependence reporting high levels of depressive symptoms may benefit from a mood management intervention.