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.

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.

Polycrystalline CVD Diamond Films with High Electrical Mobility.

Advances in the deposition process have led to dramatic improvements in the electronic properties of polycrystalline diamond films produced by chemical vapor deposition (CVD). It is now possible to produce CVD diamond with properties approaching those of IIa natural diamonds. The combined electron-hole mobility, as measured by transient photoconductivity at low carrier density, is 4000 square centimeters per volt per second at an electric field of 200 volts per centimeter and is comparable to that of the best single-crystal IIa natural diamonds. Carrier lifetimes measured under the same conditions are 150 picoseconds for the CVD diamond and 300 picoseconds for single-crystal diamond. The collection distance at a field of 10 kilovolts per centimeter is 15 micrometers for the CVD diamond as compared to 30 micrometers for natural diamonds. The electrical qualities appear to correlate with the width of the diamond Raman peak. Also, although the collection distance at the highest fields in the films nearly equals the average grain size, there is no evidence of deleterious grain boundary effects.

Electrical Transport Properties of Undoped CVD Diamond Films.

Polycrystalline diamond films synthesized by microwave-assisted chemical vapor deposition (MACVD) were examined with transient photoconductivity, and two fundamental electrical transport properties, the carrier mobility and lifetime, were measured. The highest mobility measured is 50 centimeters squared per volt per second at low initial carrier densities (<10(15) per cubic centimeter). Electron-hole scattering causes the carrier mobility to decrease at higher carrier densities. Although not measured directly, the carrier lifetime was inferred to be 40 picoseconds. The average drift length of the carriers is smaller than the average grain size and appears to be limited by defects within the grains. The carrier mobility in the MACVD films is higher than values measured in lower quality dc-plasma films but is much smaller than that of single-crystal natural diamond.

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.

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.

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.

Quality of prenatal care; selected social, behavioral, and biomedical factors; and birth weight.

Two hundred two poor, mainly black women were studied to assess the effects of selected social, behavioral, and biologic factors on birth weight. A path analysis was used to model hypotheses about the interrelationships among these variables. Six sociocultural factors had direct paths to quality of prenatal care: amount of insurance, delay in telling others about the pregnancy, attitudes toward health professionals, month of gestation in which the pregnancy was suspected, perception of the importance of prenatal care, and initial attitude toward the pregnancy. Together, these factors accounted for 64% of the variance in the quality of prenatal care received. Four variables had direct paths to birth weight: month in which the pregnancy was suspected, quality of prenatal care, hypertension, and substance abuse, which together accounted for 13% of the variance in birth weight. The key findings were the relative impact that the quality of prenatal care, especially the source of care, had on birth weight, and the potential for improving birth outcomes by addressing the negative effects of underlying social factors.

Effects of stress and characteristic adaptability on semen quality in healthy men.

Semen from 28 healthy volunteers was assessed for basic semen measure and percent of abnormal morphologic forms every 2 weeks for 6 months. Concurrent self-reports were obtained on abstinence, frequency of ejaculation, health behavior and status, experienced stress, social support, and life events. A single assessment of characteristic adaptability (ego resiliency) also was obtained. Significant between-subject positive correlations were reported among selected semen measures, abstinence, and ego-resiliency. Stress was correlated negatively with semen measures of volume and percent normal morphologic forms.

Variation of movement characteristics with washing and capacitation of spermatozoa. II. Multivariate statistical analysis and prediction of sperm penetrating ability.

Fifty semen samples were studied by computer-assisted semen analysis before testing in the sperm penetration assay (SPA). Twenty-one concentration and movement measurements were obtained from each sample on sperm in semen, after washing and swim-up, and again after an 18-hour capacitation period. Discriminant analysis was then used to define a function from these measurements that would classify the SPA results as above or below a 10% penetration rate. A significant function was identified using the following variables: sperm concentration and motility in semen, and mean curvilinear velocity, linearity, and amplitude of lateral head displacement of washed sperm. Movement measurements of capacitated spermatozoa were not useful predictors in this analysis. The overall accuracy of this function for predicting SPA results was 72%. These findings demonstrate that computer-derived measurements of sperm movement provide biologically useful information regarding sperm function, and, in addition, emphasize the importance of multivariate techniques in the analysis and description of human sperm motion.

Variation of semen measures within normal men.

Variation in semen measures was assessed bimonthly in 15 healthy men over a 6-month period. Average within-subject coefficients of variation for sperm count, morphologic features, motility, and semen volume demonstrate considerable variation. Each day of abstinence increased the volume by an increment of 0.62 ml, the count by 17.6 X 10(6)/ml, and motility by 1.2%. Sperm count and semen volume correlated positively within subjects. Intraclass and serial correlations of semen measures provided an empirical clinical guide to the number and spacing of specimens. Three specimens spaced no more than 2 weeks apart established a reliable semen profile. Findings can be applied to basic research and clinical practice.

Stability of basic semen measures and abnormal morphology within individuals.

Semen from 15 healthy volunteers was assessed for basic semen measures every 2 weeks over a 6-month period to determine the relative stability of these factors. The parameters were: sperm count, semen volume, sperm motility, and normal morphology, along with the type of abnormal morphologic forms. Basic semen measures were generally more stable than the morphologic forms. Using three samples, seven semen factors (sperm count, normal morphology, semen volume, sperm motility, microcephaly, tapering and round tail) were found to be stable and contributed to the identification of the fifteen individuals with a classification accuracy of 75.0%. While individuals do have characteristic patterns of spermatogenesis, the biologic basis for these findings is as yet undetermined.

Punishing pregnant drug users: enhancing the flight from care.

One hundred forty-two low income women were interviewed postpartum to determine their attitudes regarding the potential effects of a punitive law on the behavior of substance-using pregnant women. The convenience sample was primarily black (85.2%) and single (81%) and 14.8% admitted use of illicit drugs during pregnancy. A goodness-of-fit chi-square analysis revealed that subjects believed a punitive law would be a significant deterrent to substance-using gravida seeking prenatal care, drug testing or drug treatment (P < 0.01). Comments indicated that substance-using pregnant women would 'go underground' to avoid detection and treatment for fear of incarceration and loss of their children.

Maternal recall of alcohol, cocaine, and marijuana use during pregnancy.

Alcohol, cocaine, and marijuana use during pregnancy was reported antenatally and at 13 months postpartum by 361 black inner city mothers. The two reports were moderately related for all three substances, but levels reported retrospectively were substantially higher. MAST scores did not differ for the two interviews. Most of the correlations of the antenatal and retrospective reports with maternal and infant characteristics were similar in magnitude; those that differed were somewhat stronger for the antenatal measures. Although the retrospective reports may provide a better indication of mean levels of fetal exposure, they may be less precise in rank ordering among individuals for purposes of correlational analysis. Women with higher MAST scores were particularly prone to report higher levels of both alcohol and cocaine when interviewed retrospectively, and more severely depressed mothers were more likely to report higher levels retrospectively for all three substances. These data suggest that women reporting more than 1.3 drinks/week antenatally (AA/day greater than 0.1) may actually be drinking at levels at 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.

Clinical implications of amniotic fluid alpha-fetoprotein in twin pregnancy.

Amniotic fluid alpha-fetoprotein (AF-AFP) was measured in 68 pairs of normal twins. Acetylcholinesterase (ACHE) was measured in 23 of those pairs. A significant difference in AF-AFP levels was found in 9/49 (19.4%) of twin pairs of the same sex and 9/19 (47.3%) of twin pairs of opposite sexes (P = .015). Differences in fetal size or gestational age at amniocentesis did not influence the rate of discordant AFP results. ACHE activity was identical in all amniotic fluid samples in twin pairs. In five additional patients, fetal anomalies (three), fetal death or fetal blood in the sample could have affected AFP levels, which were found to be discordant in three of them. Using fetal sex to represent zygosity, the study indicated that discordance in AF-AFP is more common in dizygous twins. The odds ratio for having a discordant AFP result if twins are of different sexes was 4.0. Implications of our data are: (1) in same-sex twins, discordance between sacs is less common, even if only one fetus is affected; (2) the difference in AFP results in twins of the same sex and of different sexes suggests variability in AFP transfer between twin gestational sacs; and (3) ACHE readily diffuses between sacs and cannot be used to determine which twin has an abnormality.

Pregnancy, human papillomavirus and cervical intraepithelial neoplasia.

Human papillomavirus (HPV) has been implicated in the development of cervical intraepithelial neoplasia (CIN). To test the hypothesis that the known relationship between HPV and CIN might be modified by the altered immune status of pregnancy the cytologic, colposcopic and histologic findings in 176 pregnant and 515 nonpregnant patients referred to a colposcopy clinic were prospectively compared. No difference between the two groups was found regarding the frequency with which CIN and HPV were detected cytologically, colposcopically and histologically. Confidence intervals for the probability of CIN in the presence of HPV for the two groups were calculated. At the 80% confidence interval the two groups were reassuringly similar. Pregnancy did not alter the relationship of CIN to HPV. Despite the relatively small size of our study population, it is unlikely that a larger study would demonstrate a difference. Interestingly a 3% cervical carriage rate of HPV in pregnancy was demonstrated. What, if any, effect this has upon the unborn child is unknown at this time.

History of in utero cocaine exposure in language-delayed children.

To determine whether children with language delays are more likely to have been exposed to cocaine in utero than children with normal language development, a case-control study was undertaken. Based on routine office screening in our primary-care clinic over a 1-year period, we identified 29 consecutive children, aged 24 to 48 months, as language-delayed. They were compared with an approximate 2:1 match of children without language delay who had been seen in the clinic on the same days and who were of similar age. There was more reported cocaine use during pregnancy (six of 29, 21%) among the language-delayed children than among the controls (five of 71, 7%). This difference is statistically significant (P < 0.05, chi 2 = 3.92; odds ratio = 3.4 +/- 2.2). Discriminant analysis revealed that both cocaine and nicotine exposure were associated with delayed language development--with an unexpected negative, i.e., an antagonistic, protective, interactive effect (F[3,96] = 4.66, R2 = 12.7%, P < .005); neither gender nor caretaker contributed to language development in this sample. These results suggest that children with language delay detected in a clinical setting are more likely to have been exposed in utero to cocaine than children with normal language development. Prenatal cocaine exposure should be a risk factor in monitoring development in children.