Changes in cortical bone response to high-fat diet from adolescence to adulthood in mice.

UNLABELLED: Diabetic obesity is associated with increased fracture risk in adults and adolescents. We find in both adolescent and adult mice dramatically inferior mechanical properties and structural quality of cortical bone, in agreement with the human fracture data, although some aspects of the response to obesity appear to differ by age. INTRODUCTION: The association of obesity with bone is complex and varies with age. Diabetic obese adolescents and adult humans have increased fracture risk. Prior studies have shown reduced mechanical properties as a result of high-fat diet (HFD) but do not fully address size-independent mechanical properties or structural quality, which are important to understand material behavior. METHODS: Cortical bone from femurs and tibiae from two age groups of C57BL/6 mice fed either HFD or low-fat diet (LFD) were evaluated for structural and bone turnover changes (SEM and histomorphometry) and tested for bending strength, bending stiffness, and fracture toughness. Leptin, IGF-I, and non-enzymatic glycation measurements were also collected. RESULTS: In both young and adult mice fed on HFD, femoral strength, stiffness, and toughness are all dramatically lower than controls. Inferior lamellar and osteocyte alignment also point to reduced structural quality in both age groups. Bone size was largely unaffected by HFD, although there was a shift from increasing bone size in obese adolescents to decreasing in adults. IGF-I levels were lower in young obese mice only. CONCLUSIONS: While the response to obesity of murine cortical bone mass, bone formation, and hormonal changes appear to differ by age, the bone mechanical properties for young and adult groups are similar. In agreement with human fracture trends, adult mice may be similarly susceptible to bone fracture to the young group, although cortical bone in the two age groups responds to diabetic obesity differently.

Embedded binary eutectic alloy nanostructures: a new class of phase change materials.

Phase change materials are essential to a number of technologies ranging from optical data storage to energy storage and transport applications. This widespread interest has given rise to a substantial effort to develop bulk phase change materials well suited for desired applications. Here, we suggest a novel and complementary approach, the use of binary eutectic alloy nanoparticles embedded within a matrix. Using GeSn nanoparticles embedded in silica as an example, we establish that the presence of a nanoparticle/matrix interface enables one to stabilize both nanobicrystal and homogeneous alloy morphologies. Further, the kinetics of switching between the two morphologies can be tuned simply by altering the composition.

Above-bandgap voltages from ferroelectric photovoltaic devices.

In conventional solid-state photovoltaics, electron-hole pairs are created by light absorption in a semiconductor and separated by the electric field spaning a micrometre-thick depletion region. The maximum voltage these devices can produce is equal to the semiconductor electronic bandgap. Here, we report the discovery of a fundamentally different mechanism for photovoltaic charge separation, which operates over a distance of 1-2 nm and produces voltages that are significantly higher than the bandgap. The separation happens at previously unobserved nanoscale steps of the electrostatic potential that naturally occur at ferroelectric domain walls in the complex oxide BiFeO(3). Electric-field control over domain structure allows the photovoltaic effect to be reversed in polarity or turned off. This new degree of control, and the high voltages produced, may find application in optoelectronic devices.

Reduced size-independent mechanical properties of cortical bone in high-fat diet-induced obesity.

Overweight and obesity are rapidly expanding health problems in children and adolescents. Obesity is associated with greater bone mineral content that might be expected to protect against fracture, which has been observed in adults. Paradoxically, however, the incidence of bone fractures has been found to increase in overweight and obese children and adolescents. Prior studies have shown some reduced mechanical properties as a result of high-fat diet (HFD) but do not fully address size-independent measures of mechanical properties, which are important to understand material behavior. To clarify the effects of HFD on the mechanical properties and microstructure of bone, femora from C57BL/6 mice fed either a HFD or standard laboratory chow (Chow) were evaluated for structural changes and tested for bending strength, bending stiffness and fracture toughness. Here, we find that in young, obese, high-fat fed mice, all geometric parameters of the femoral bone, except length, are increased, but strength, bending stiffness, and fracture toughness are all reduced. This increased bone size and reduced size-independent mechanical properties suggests that obesity leads to a general reduction in bone quality despite an increase in bone quantity; yield and maximum loads, however, remained unchanged, suggesting compensatory mechanisms. We conclude that diet-induced obesity increases bone size and reduces size-independent mechanical properties of cortical bone in mice. This study indicates that bone quantity and bone quality play important compensatory roles in determining fracture risk.

Theory of nanocluster size distributions from ion beam synthesis.

Ion beam synthesis of nanoclusters is studied via both kinetic Monte Carlo simulations and the self-consistent mean-field solution to a set of coupled rate equations. Both approaches predict the existence of a steady-state shape for the cluster-size distribution that depends only on a characteristic length determined by the effective diffusion coefficient, the ion solubility, and the volumetric ion flux. The average cluster size in the steady-state regime is determined by the implanted species or matrix interface energy.

Measurement of the toughness of bone: a tutorial with special reference to small animal studies.

Quantitative assessment of the strength and toughness of bone has become an integral part of many biological and bioengineering studies on the structural properties of bone and their degradation due to aging, disease and therapeutic treatment. Whereas the biomechanical techniques for characterizing bone strength are well documented, few studies have focused on the theory, methodology, and various experimental procedures for evaluating the fracture toughness of bone, i.e., its resistance to fracture, with particular reference to whole bone testing in small animal studies. In this tutorial, we consider the many techniques for evaluating toughness and assess their specific relevance and application to the mechanical testing of small animal bones. Parallel experimental studies on wild-type rat and mouse femurs are used to evaluate the utility of these techniques and specifically to determine the coefficient of variation of the measured toughness values.

The true toughness of human cortical bone measured with realistically short cracks.

Bone is more difficult to break than to split. Although this is well known, and many studies exist on the behaviour of long cracks in bone, there is a need for data on the orientation-dependent crack-growth resistance behaviour of human cortical bone that accurately assesses its toughness at appropriate size scales. Here, we use in situ mechanical testing to examine how physiologically pertinent short (<600 microm) cracks propagate in both the transverse and longitudinal orientations in cortical bone, using both crack-deflection/twist mechanics and nonlinear-elastic fracture mechanics to determine crack-resistance curves. We find that after only 500 microm of cracking, the driving force for crack propagation was more than five times higher in the transverse (breaking) direction than in the longitudinal (splitting) direction owing to major crack deflections/twists, principally at cement sheaths. Indeed, our results show that the true transverse toughness of cortical bone is far higher than previously reported. However, the toughness in the longitudinal orientation, where cracks tend to follow the cement lines, is quite low at these small crack sizes; it is only when cracks become several millimetres in length that bridging mechanisms can fully develop leading to the (larger-crack) toughnesses generally quoted for bone.

Large melting-point hysteresis of Ge nanocrystals embedded in SiO2.

The melting behavior of Ge nanocrystals embedded within SiO2 is evaluated using in situ transmission electron microscopy. The observed melting-point hysteresis is large (+/-17%) and nearly symmetric about the bulk melting point. This hysteresis is modeled successfully using classical nucleation theory without the need to invoke epitaxy.

Optical detection and ionization of donors in specific electronic and nuclear spin States.

We resolve the remarkably sharp bound exciton transitions of highly enriched 28Si using a single-frequency laser and photoluminescence excitation spectroscopy, as well as photocurrent spectroscopy. Well-resolved doublets in the spectrum of the 31P donor reflect the hyperfine coupling of the electronic and nuclear donor spins. The optical detection of the nuclear spin state, and selective pumping and ionization of donors in specific electronic and nuclear spin states, suggests a number of new possibilities which could be useful for the realization of silicon-based quantum computers.

Evidence for p-type doping of InN.

The first evidence of successful p-type doping of InN is presented. It is shown that InN:Mg films consist of a p-type bulk region with a thin n-type inversion layer at the surface that prevents electrical contact to the bulk. Capacitance-voltage measurements indicate a net concentration of ionized acceptors below the -type surface. Irradiation with 2 MeV He+ ions is used to convert the bulk of InN:Mg from p to n-type, at which point photoluminescence is recovered. The conversion is well explained by a model assuming two parallel conducting layers (the surface and the bulk) in the films.

Deep-ultraviolet Raman spectroscopy study of the effect of aging on human cortical bone.

The age-related deterioration in bone quality and consequent increase in fracture incidence is an obvious health concern that is becoming increasingly significant as the population ages. Raman spectroscopy with deep-ultraviolet excitation (244 nm) is used to measure vibrational spectra from human cortical bone obtained from donors over a wide age range (34-99 years). The UV Raman technique avoids the fluorescence background usually found with visible and near-infrared excitation and, due to resonance Raman effects, is particularly sensitive to the organic component of bone. Spectral changes in the amide I band at 1640 cm(-1) are found to correlate with both donor age and with previously reported fracture toughness data obtained from the same specimens. These results are discussed in the context of possible changes in collagen cross-linking chemistry as a function of age, and are deemed important to further our understanding of the changes in the organic component of the bone matrix with aging.

Effects of polar solvents on the fracture resistance of dentin: role of water hydration.

Although healthy dentin is invariably hydrated in vivo, from a perspective of examining the mechanisms of fracture in dentin, it is interesting to consider the role of water hydration. Furthermore, it is feasible that exposure to certain polar solvents, e.g., those found in clinical adhesives, can induce dehydration. In the present study, in vitro deformation and fracture experiments, the latter involving a resistance-curve (R-curve) approach (i.e., toughness evolution with crack extension), were conducted in order to assess changes in the constitutive and fracture behavior induced by three common solvents-acetone, ethanol and methanol. In addition, nanoindentation-based experiments were performed to evaluate the deformation behavior at the level of individual collagen fibers and ultraviolet Raman spectroscopy to evaluate changes in bonding. The results indicate a reversible effect of chemical dehydration, with increased fracture resistance, strength, and stiffness associated with lower hydrogen bonding ability of the solvent. These results are analyzed both in terms of intrinsic and extrinsic toughening phenomena to further understand the micromechanisms of fracture in dentin and the specific role of water hydration.

Nonlinear components of age-related change in sleep initiation.

BACKGROUND: Although primary studies suggest that ability to initiate sleep declines as people age, no systematic literature review has addressed the age(s) at which adults experience the greatest change in their ability to initiate sleep. OBJECTIVE: To explore whether there are any points in time across the adult life span when the rate of change in ability to initiate sleep increases or decreases. METHODS: Mathematical modeling was used to generate data points from information about central tendency, variance, and correlations between age and time to sleep onset provided by seven research reports. The reports represent 258 subjects ages 17 to 91 years. Smoothing splines were used to identify inflection points suggestive of major changes in sleep initiation across the life span. RESULTS: Two mathematical models were generated. One model suggested that inflection points may exist around ages 30 and 50 years, respectively. With this model, the amount of time until sleep onset increased until the age of 30 years, but was unchanged from ages 30 to 50 years. Ability to initiate sleep appeared to decline steadily after the age of 50 years. The second model, with a p value of 0.05, lacked adequate power to identify a significant nonlinear trend. CONCLUSIONS: Decline in ability to initiate sleep may not occur at a steady rate over the adult life span. Further research is needed to pinpoint thresholds of change and possible gender differences in thresholds.

Age-related changes in initiation and maintenance of sleep: a meta-analysis.

The purpose of this meta-analysis was to determine the magnitude of change over the adult life span in four key sleep characteristics and to explore research design features that may account for variability in reported age-related sleep change. Forty-one published studies (combined N = 3293) provided 99 correlational effect sizes. Waking frequency and duration increased with age as previously concluded by narrative reviewers. Although narrative reviewers were less certain whether nighttime sleep amount or the ability to initiate sleep decreased with age, the meta-analysis suggested that both decreased. When sleep variables were measured by polysomnography rather than self-report, larger age-related changes were found. Few researchers who studied normal sleep controlled for important health moderators or studied women.

Relation of maternal age and pattern of pregnancy drinking to functionally significant cognitive deficit in infancy.

Prospective studies of the effects of prenatal alcohol exposure on development have focused primarily on the detection of subtle deficits. This study was designed to extend those findings by evaluating dose-response, functional significance, and pattern of drinking in greater detail. 480 African-American infants, recruited to overrepresent prenatal exposure at moderate-to-heavy levels, were assessed. For the five outcomes tested, nonparametric and hockey stick regression analyses both indicated essentially no relation between pregnancy drinking and developmental outcome below a median threshold of 0.5 oz absolute alcohol/day, with the impact of the exposure increasing gradually above threshold. Functional deficit was defined in terms of performance in the bottom 10th percentile of the distribution. For four of the five outcomes tested, there was no increased incidence of functionally significant deficit in infants born to moderate-to-heavy drinking mothers <30 years old, whereas those born to older drinking mothers were 2 to 5 times more likely to be functionally impaired. Among the infants exposed above threshold, functionally significant deficits were seen primarily in those whose mothers averaged at least 5 drinks/occasion on an average of at least once/week. By contrast, a history of alcohol abuse was not related to functional deficit. These data suggest that efforts to reduce the incidence of alcohol-related functional impairment should specifically target the older mother who engages in intermittent heavy drinking during pregnancy.

Neonatal outcome following methadone exposure in utero.

To examine the relationship between maternal methadone exposure and neonatal head circumference and abstinence syndrome, we examined the records of 172 opiate-addicted gravidas enrolled in a methadone maintenance program in an urban hospital over a 2-year period. Higher doses of methadone in the third trimester were associated with increased head circumference reflecting both increased gestational duration and improved overall growth. Neonatal withdrawal was positively correlated with gestational age at delivery and race, with nonblack infants exhibiting higher neonatal abstinence scores than blacks following adjustment for maternal dose and gestational age at delivery. Selection of optimal methadone dosage is a complex problem in which the favorable neurobehavioral outcome associated with increased growth and gestational age must be weighed against the risks associated with more severe neonatal withdrawal. Our findings of improved overall fetal growth and gestational duration associated with higher methadone doses suggest that more liberal methadone dosing in pregnancy may improve long-term neonatal outcome.

Effects of case management on retention in prenatal substance abuse treatment.

Participation in substance abuse treatment during pregnancy is associated with improved pregnancy outcomes. Case management has been proposed as one way to reduce barriers to receiving and continuing treatment. An evaluation was conducted on a case management program to retain pregnant women in drug treatment. Two hundred twenty-five pregnant women received case management services consisting of home visits, telephone counseling, transportation, and referral. All women contacted a substance abuse treatment center and most (56%) obtained treatment during pregnancy. Sociodemographic factors, personal and family history of substance use and drug treatment, protective services involvement, history of physical and sexual abuse, and need for tangible resources were assessed. Charts were reviewed at the substance abuse treatment center for number of visits and urine toxicology reports, and at the hospital for pregnancy outcome. Data were analyzed by LISREL path analysis. Five factors had significant path correlations to prenatal attendance at the substance abuse treatment center: history of protective services involvement, number of drugs ever used, currently receiving methadone, intensity of case management, and receiving transportation to drug treatment appointments. We conclude that case management, including providing transportation, contributes significantly to retention in substance abuse treatment during pregnancy.

Has awareness of the alcohol warning label reached its upper limit?

Has awareness of the alcoholic beverage warning label reached its maximum? This study tracks changes in the level of awareness among a sample of 7334 inner-city African-American gravidas seeking prenatal care between May 1989 and June 1993. Previously, we found that a significant increase in awareness of the warning label occurred in March 1990. In the current analysis over a 50-month period, the level of awareness continued to increase through December 1992 and then leveled off, suggesting a negatively accelerated growth function. The logistic function fitted to the awareness curve predicts that the upper limit of awareness in this population has been reached (the predicted upper limit being 81.5%). In addition a logit regression analysis showed that women who did not know about the warning label were more likely to be over 29 years of age. Heavier drinkers were 1.25 times more likely to be aware of the label. Among those drinkers who were not aware of the label, 30% drank at both conception and antenally, thus putting their fetus at high risk for alcohol-related birth defects.

Heeding the alcoholic beverage warning label during pregnancy: multiparae versus nulliparae.

OBJECTIVE: We compared the impact of the Federal Alcoholic Beverage Warning Label on multiparae (women with at least one previous live birth) and nulliparae (women with no previous live births). The label, implemented on November 18, 1989, urges women not to drink during pregnancy because of the risk of birth defects. If multiparae drank during prior pregnancies, delivering apparently normal babies, we hypothesized that the warning might be less salient for them. METHOD: We studied 17,456 inner city black gravidas seen between September 1986 and September 1993 at one antenatal clinic. Time series analysis (ARIMA) examined trends in monthly means of antenatal drinking scores (alcohol consumption adjusted for weeks' gestation, age, parity and periconceptional drinking). RESULTS: For nulliparae (n = 7,349), reported drinking began to show a significant decline in June 1990, 7 months after the implementation of the warning label (t = 2.00, p < .04). In contrast, multiparae (n = 10,107) showed no change in reported drinking (t = 1.23) postlabel. CONCLUSIONS: Given previous results that multiparae drink more and that heavier drinkers are ignoring the warning label, these data are very distressing and suggests the importance of targeting multiparae for intensive prevention efforts.

Autoimmunity to collagen in human lung cancer.

Autoantibodies have been described in human cancer patients as well as in animal models of malignancy. The extracellular matrix and especially basement membranes act as barriers for tumor cell invasion. Collagen, particularly types I, III, and IV, are major constituents of the extracellular matrix. We tested the hypothesis that autoimmunity to collagen antigens is present in lung cancer. Sera from 67 patients with lung cancer and 50 reference subjects were tested for anticollagen antibodies by using purified human collagen types I-V and for antibodies binding human cartilage aggrecan proteoglycan. Antibody levels were determined by using ELISA. The relationship of serum levels of these antibodies to patient survival, histology, treatment response, disease stage, and pack years of smoking was examined by using multiple regression and discriminant function analyses. A subgroup of 45 patients in whom a smoking history was available was analyzed separately. Within 1 month of the initiation of therapy, mean serum levels of antibodies binding fibrillar collagen types I-III and V were significantly higher (P < 0.025) than were those in control sera (43.2% of patients positive for one or more anticollagen antibodies). Antibodies binding aggrecan proteoglycan were not different between patients and control sera. In the lung cancer patients, the levels of serum antibodies binding types IV and V collagens contributed to the variance of progression-free survival days, survival days, and the duration of favorable response in opposite directions. Histological cell type contributed to the variance in the level of serum antibody binding collagen types IV and V. Lower levels of antibody binding type IV and higher levels of antibody binding type V were associated with small cell carcinoma. The pack-years of smoking only contributed to the variance in the level of serum antibody binding type V collagen. We conclude that autoantibodies to fibrillar collagen antigens are present frequently in lung cancer patients, and their levels may be related to histological cell type and to the duration of the response to treatment.