Early childhood lead exposure is not reflected in adult bone lead: Results of a sub-cohort of African American women in the Cincinnati lead study.

INTRODUCTION: Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues. METHODS: 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health. RESULTS: BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was -2.0 ± 8.6 µgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb). DISCUSSION: Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb.

Arginine site 264 in murine estrogen receptor-α is dispensable for the regulation of the skeleton.

Mutation of arginine 264 in ERα has been shown to abrogate rapid membrane ERα-mediated endothelial effects. Our novel finding that mutation of R264 is dispensable for ERα-mediated skeletal effects supports the concept that R264 determines tissue specificity of ERα. Estrogen protects against bone loss but is not a suitable treatment due to adverse effects in other tissues. Therefore, increased knowledge regarding estrogen signaling in estrogen-responsive tissues is warranted to aid the development of bone-specific estrogen treatments. Estrogen receptor-α (ERα), the main mediator of estrogenic effects in bone, is widely subjected to posttranslational modifications (PTMs). In vitro studies have shown that methylation at site R260 in the human ERα affects receptor localization and intracellular signaling. The corresponding amino acid R264 in murine ERα has been shown to have a functional role in endothelium in vivo, although the methylation of R264 in the murine gene is yet to be empirically demonstrated. The aim of this study was to investigate whether R264 in ERα is involved in the regulation of the skeleton in vivo. Dual-energy X-ray absorptiometry (DEXA) analysis at 3, 6, 9, and 12 mo of age showed no differences in total body areal bone mineral density (BMD) between R264A and wild type (WT) in either female or male mice. Furthermore, analyses using computed tomography (CT) demonstrated that trabecular bone mass in tibia and vertebra and cortical thickness in tibia were similar between R264A and WT mice. In addition, R264A females displayed a normal estrogen treatment response in trabecular bone mass as well as in cortical thickness. Furthermore, uterus, thymus, and adipose tissue responded similarly in R264A and WT female mice after estrogen treatment. In conclusion, our novel finding that mutation of R264 in ERα does not affect the regulation of the skeleton, together with the known role of R264 for ERα-mediated endothelial effects, supports the concept that R264 determines tissue specificity of ERα.NEW & NOTEWORTHY Mutation of arginine 264 in ERα has been shown to abrogate rapid membrane ERα-mediated endothelial effects. Our novel finding that mutation of R264 is dispensable for ERα-mediated skeletal effects supports the concept that R264 determines tissue specificity of ERα.

Identification of antemortem and postmortem fractures in a complex environment by FTIR spectroscopy based on a rabbit tibial fracture self-control model.

The identification of antemortem and postmortem fractures is a critical and challenging task for forensic researchers. Based on our preliminary studies, we explored whether the combination of Fourier transform infrared spectroscopy (FTIR) and chemometrics can identify antemortem and postmortem fractures in complex environments. The impacts of the four environments on the bone spectrum were analyzed by principal component analysis (PCA). It was found that the bone degradation rate in the submerged and ground surface (GS) environments was higher than that in the buried and constant temperature and moisture (CTM) environments. Additionally, the bone degradation rate in buried environment higher than that in the CTM environment. The average spectrum, PCA and partial least squares discriminant analysis (PLS-DA) results all revealed that there were significant differences between the antemortem fracture and the remaining three groups in a complex environment. Compared with the antemortem fracture, the antemortem fracture control (AFC) and postmortem fracture control (PFC) tended to be more similar to the postmortem fracture. According to the loading plot, amide I and amide II were the main components that contributed to the identification of the antemortem fracture, AFC, postmortem fracture, and PFC. Finally, we established a differential model for the antemortem and postmortem fractures (an accuracy of 96.9%), and a differentiation model for the antemortem fracture, AFC, postmortem fracture, and PFC (an accuracy of 87.5%). In conclusion, FTIR spectroscopy is a reliable tool for the identification of antemortem and postmortem fractures in complex environments.

A novel, 4-h DNA extraction method for STR typing of casework bone samples.

Bones are often found in mass grave crime scene. To increase DNA identification success rates, a highly efficient DNA extraction method should be selected. Several DNA extraction methods for human bones have been published yet never been systematically compared, and some are time-consuming or complex. As such, a quick and highly efficient DNA extraction method was developed and compared with three published methods (Hi-Flow silica-based, total demineralization (TD) and PrepFiler BTA) using 70 fresh and 22 casework bones from different body parts. The highest median DNA concentrations were obtained from developed method (135.85 ng/µL and 0.224 ng/µL for fresh and casework bones, respectively). For residual PCR inhibitors, the threshold cycle (Ct) of the internal positive control (IPC) showed that developed method and PrepFiler BTA removed most PCR inhibitors. Similarly, 95.45% of casework STR profiles obtained using the developed protocol meet the standard requirements for Australian National Criminal Investigative DNA Database (NCIDD) entry, followed by 86.35% using TD, 81.82% using PrepFiler BTA, and 45.45% using Hi-Flow. Additionally, DNA extracts from seven different bones revealed that the 1st distal phalange of the hand contained the highest DNA concentration of 338.43 ng/µL, which was three times higher than the tibia and femur. Our findings suggest that developed method was highly efficient for casework bone analysis. It significantly reduced the extraction processing time down to 4 h and is two to four times cheaper compared with other methods. In practice, both the extraction method and the bone sampling must be considered by a forensic DNA analyst to increase the chances of successful identification.

Long TE PRESS and STEAM for measuring the triglyceride glycerol CH2 protons at 3 T.

The glycerol methylene proton resonances (4-4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J-coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R2  = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.

Dietary supplemental vitamin D3 enhances phosphorus absorption and utilisation by regulating gene expression of related phosphate transporters in the small intestine of broilers.

The present study was carried out to evaluate the effect of dietary supplemental vitamin D3 (VD3) on P absorption and utilisation as well as its related mechanisms in the small intestine of broilers. A total of 384 1-d-old Arbor Acres male broilers were assigned randomly into four treatments following a completely randomised design with a 2 (dietary non-phytate P (NPP) contents: 0·43 and 0·22 %)×2 (dietary VD3 supplemental levels: 0 and 87·5 µg/kg) factorial arrangement. The experiment lasted for 22 d. The results showed that P contents in serum from the hepatic portal vein and tibia ash of broilers were higher (P<0·05) for 0·43 % NPP than for 0·22 % NPP. The type IIb Na-dependent phosphate cotransporter (NaP-IIb) protein expressions in the duodenum and ileum were higher (P<0·05) also for 0·43 % NPP than 0·22 % NPP. Supplementation of VD3 enhanced (P<0·05) tibia P retention rate and type III Na-dependent phosphate cotransporter (PiT)-1 protein expression in the duodenum of all broilers. Moreover, VD3 supplementation decreased (P<0·002) mortality and increased (P<0·02) serum P content from the hepatic portal vein after 4 h of feeding, tibia ash content, tibia ash P content and protein expressions of NaP-IIb and PiT-1 in the jejunum of broilers fed diet with 0·22 % NPP. Thus, dietary supplemental VD3 promoted intestinal P absorption and bone P utilisation, and this effect might be associated with enhanced PiT-1 levels in the duodenum and PiT-1 and NaP-IIb levels in the jejunum respectively when dietary NPP is limiting.

Resveratrol reverses the negative effect of smoking on peri-implant repair in the tibia of rats.

OBJECTIVES: Innovative approaches capable to improve peri-implant bone repair are relevant in the presence of smoking, a risk factor for healing around implants. This study investigated the effect of resveratrol (RESV) on peri-implant repair, and its influence on bone-related markers in rats submitted to cigarette smoking inhalation (CSI). MATERIALS AND METHODS: One titanium implant was inserted in each tibiae of rats assigned to CSI+RESV (n:18); CSI+placebo (n:18); and non-CSI (n:18). One implant was removed for counter torque, and the peri-implant tissue was collected for mRNA quantification of BMP-2, OPN, Runx2, Lrp-5, Osx, ß-catenin, Dkk1, OPG, and RANKL. The other tibia was submitted to microCT to measure: bone volume, bone porosity, trabecular spacing, trabecular thickness, and bone-implant contact (BIC). RESULTS: No differences were detected between counter torque in CSI+RESV and non-CSI group (p > 0.05), whereas CSI+placebo group presented lower values when compared to the others (p < 0.05). RESV improved the BIC in CSI rats without differences when compared to non-CSI group (p > 0.05), whereas CSI+placebo showed reduced BIC when compared to the other groups (p < 0.05). RESV reduced RANKL/OPG and Lrp-5 levels and increased ß-catenin in CSI rats when compared to CSI+placebo (p < 0.05). CONCLUSION: Although further investigations should be considered using oral models of dental implants, within the limits of the present study, it was concluded that RESV reverses the negative effects of smoking in the peri-implant repair, benefiting the modulation of bone-related markers.

Biomechanical Stability and Osteogenesis in a Tibial Bone Defect Treated by Autologous Ovine Cord Blood Cells-A Pilot Study.

The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA.

Isolation and Characterization of a Novel Sialoglycopeptide Promoting Osteogenesis from Gadus morhua Eggs.

Gadus morhua eggs contain several nutrients, including polyunsaturated fatty acids, lecithin and glycoproteins. A novel sialoglycopeptide from the eggs of G. morhua (Gm-SGPP) was extracted with 90% phenol and purified by Q Sepharose Fast Flow (QFF) ion exchange chromatography, followed by S-300 gel filtration chromatography. Gm-SGPP contained 63.7% carbohydrate, 16.2% protein and 18.6% N-acetylneuraminic acid. High-performance size exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that Gm-SGPP is a 7000-Da pure sialoglycopeptide. ß-elimination reaction suggested that Gm-SGPP contained N-glycan units. Amino acid N-terminal sequence analysis indicated the presence of Ala-Ser-Asn-Gly-Thr-Gln-Ala-Pro amino acid sequence. Moreover, N-glycan was connected at the third Asn location of the peptide chain through GlcNAc. Gm-SGPP was composed of D-mannose, D-glucuronic acid and D-galactose. Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR) and methylation analysis were performed to reveal the structure profile of Gm-SGPP. In vitro results showed that the proliferation activity of MC3T3-E1 cells was significantly promoted by Gm-SGPP. In vivo data revealed that Gm-SGPP increased the calcium and phosphorus content of tibias and promoted longitudinal bone growth in adolescent rats.

Human Bone Paleoproteomics Utilizing the Single-Pot, Solid-Phase-Enhanced Sample Preparation Method to Maximize Detected Proteins and Reduce Humics.

Sample preparation has become an important part of bone proteomics and paleoproteomics and remains one of the major challenges to maximizing the number of proteins characterized from bone extractions. Most paleoproteomic studies have relied on in-solution digestion with the inclusion of filter-aided sample preparation (FASP) as effective methods to detect the proteome. However, neither of these are optimal because few proteins have been detected utilizing only in-solution digestion and the molecular weight cutoff of FASP may miss remaining fragments of proteins in fossil bone. The recently developed single-pot, solid-phase-enhanced sample preparation (SP3) overcomes these issues by not relying on molecular weight while still controlling where the proteins are digested. Here, historical human bones were extracted with either 500 mM tetrasodium EDTA or 400 mM ammonium phosphate dibasic, 200 mM ammonium bicarbonate, 4 M guanidine HCl and digested with the SP3 method. Across all samples, 78 ± 7 (400-200-4) and 79 ± 17 (EDTA) protein accessions were identified, including previously difficult to detect proteins such as osteopontin. SP3 also effectively removed 90% or more of the coextracting humic substances (based on reduced absorbance) from extracted proteins. The utility of SP3 for maximizing the number of protein detections in historical bones is promising for future paleoproteomic studies.

Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Body growth, intestinal morphology and microflora of quail on diets supplemented with micronised wheat fibre.

1. Particle size reductions of fibre-rich materials alter structure, functional and digestive properties. To determine the effects of using fibre as an additive in Japanese quail rations on performance and gut physiology, a trial using micronised wheat fibre (MWF) at levels of 0.0, 5, 10 and 15 g/kg in feed was conducted. 2. Growth rate and feed efficiency were significantly improved when diets contained MWF while feed intake was not affected by levels of the fibre. As MWF content increased, the relative weight of gizzard and gastrointestinal tract (GIT) significantly increased whereas liver relative weight significantly decreased. 3. MWF inclusion significantly increased relative length of gut segments, villi height, villus thickness, the villi height to crypt depth proportion in jejunum and ileum and the number of goblet cells in different parts of intestine. 4. Tibia weight, length and ash content were increased linearly with rising MWF inclusion. Litter moisture was affected by MWF inclusions in a quadratic manner. The colony forming unit (CFU/g) of Streptococci spp. in ileal digesta was decreased with increasing MWF inclusion levels in the diet. 5. In conclusion, MWF can be used as a feed additive in quail diets and its inclusion in feed resulted in better performance, beneficial changes in intestinal microbial counts and improvements in small intestine morphology.

Non-phytate phosphorus requirement for broilers from 8 to 21 days of age under heat stress conditions.

Two trials were conducted to determine the non-phytate phosphorus (nPP) requirement for broiler under heat stress. In both trials, birds were distributed in a completely randomized 4 × 2 factorial design with four nPP concentrations: 0.25, 0.35, 0.45, and 0.55%, and two Ca supply techniques: Ca fixed at 0.899% (CaF) or varying along with nPP aiming a 2:1 Ca to nPP ratio (CaV). Both trials had eight pens/treatment, with nine and five birds/pen for exp. 1 and exp. 2, respectively. nPP concentration had no effect on feed intake (FI), body weight gain (BWG), feed conversion ratio (FCR), nor fat deposition ratio (FDR). nPP levels showed a linear effect on protein deposition ratio (PDR) only for CaF diets. The nPP levels had a significant effect, regardless the technique adopted, on tibia phosphorus (TibP), which varied quadratically, on tibia calcium (TibCa) that increased quadratically and linearly, respectively, on CaF and CaV diets, and on tibia ash (TibAsh) that showed a quadratic effect for both. No effect was observed on Ca to P ratio in the tibia (TibCa:TibP). The nPP levels showed a linear increase effect over phosphorus intake (PI), phosphorus excreted (PE), and phosphorus retained (PR), and a linear decrease effect on phosphorus retention coefficient (PRC). Therefore, the nPP requirement for broilers from 8 to 21 days of age that provided better performance and bone variables were 0.250 and 0.484%, respectively, for CaF diets and 0.250 and 0.511%, respectively, for CaV diets.

A probable case of doping in an Olympic athlete coming back from ancient Greece (V cent. B.C.).

We present here the hypothesis of doping in an athlete coming back from the ancient Greece, dating back to V century B.C. There are some bone alterations due to the sports that he probably practiced, and that are represented on the amphorae (prices of his victories) found near his sepulchre. The skeleton shows a considerable mass and bone density. The chemical analyses performed on the bone emphasized the presence of arsenic, while the X-ray and CAT scan examinations revealed a quite big sella turcica. These two aspects might have influenced the performances of this athlete, and in the same time might have provoked his death at the age of about 30 years.

Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone.

Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. INTRODUCTION: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. METHODS: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with µCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). RESULTS: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (-14 and -3%, p < 0.01, respectively) and crystallinity (-1.4 and -0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. CONCLUSION: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study.

BACKGROUND: Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. METHODS: In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. RESULTS: Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21µg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb. CONCLUSIONS: Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging.

Subchondral screw abutment: does it harm the joint cartilage? An in vivo study on sheep tibiae.

PURPOSE: Subchondral screw abutment in osteosynthesis of joint fractures is an effective method to achieve sufficient screw grip. In this study we investigated if subchondral screw placement is possible without harming the overlying subchondral plate and joint cartilage iatrogenic. MATERIALS AND METHODS: A 3.5-mm conventional steel screw was placed in the tibia of ten sheep in distances between 1 and 7 mm beneath the joint cartilage. After a follow up of two and four months, evaluation of the subchondral bone and joint cartilage was performed by means of a histological osteoarthritis score, HRpQCT imaging and determination of the glycosaminoglycan content in the cartilage. The control group was the contralateral knee of the same animal. RESULTS: Histomorphometric evaluation of the Mankin osteoarthritis score revealed no significant difference compared to the control after two (p = 0.102) and four months (p = 0.429). No correlation between distance of the screw to the cartilage and histological scoring was found (p = 0.658, R2 = 0.04 after two months and p = 0.171, R2 = 0.18 after four months). HRpQCT measurements of the subchondral thickness between screw and cartilage after two (p = 0.05) and four months (p = 0.424) showed no significant difference. Mean glycosaminoglycan content in the treatment group compared to the control after two months (p = 0.25) and four months (p = 0.523) was not significant different. CONCLUSION: In conclusion subchondral screw abutment did not damage the joint cartilage after a two- and four-month follow up in this sheep model.

Long-bone properties and development are affected by caponisation and breed in Polish fowls.

1. The aim of the study was to investigate the effects of caponisation on bone development of males of two native breeds in Poland. 2. The weight, length and cross-sectional area of tibiae and femora were measured, densitometric measurements and tests of strength were determined and dimensions were calculated. 3. Breed and caponisation did not influence bone weight and length. Higher mechanical strength of the femur was found in entire males, mainly in the Polbar breed. Tibial strength was reduced in capons of the Green Partridge breed. Maximum elastic strength was greater in the Polbar, irrespective of caponisation. Bone cross-sectional area was influenced by breed, while caponisation reduced femoral bone mineral density in both breeds. 4. Caponisation thus increased growth rate but had adverse effects on bone development. 5. Caponisation had fewer negative effects in the Polbar than in the Greenleg Partridge.

APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals.

BACKGROUND: Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. METHODS: We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. RESULTS: An interquartile range (IQR:14.23µg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: -0.11 to -0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: -0.97 to -0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: -0.11, 95%CI: -0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. CONCLUSIONS: Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

Toddler temperament and prenatal exposure to lead and maternal depression.

BACKGROUND: Temperament is a psychological construct that reflects both personality and an infant's reaction to social stimuli. It can be assessed early in life and is stable over time Temperament predicts many later life behaviors and illnesses, including impulsivity, emotional regulation and obesity. Early life exposure to neurotoxicants often results in developmental deficits in attention, social function, and IQ, but environmental predictors of infant temperament are largely unknown. We propose that prenatal exposure to both chemical and non-chemical environmental toxicants impacts the development of temperament, which can itself be used as a marker of risk for maladaptive neurobehavior in later life. In this study, we assessed associations among prenatal and early life exposure to lead, mercury, poverty, maternal depression and toddler temperament. METHODS: A prospective cohort of women living in the Mexico City area were followed longitudinally beginning in the second trimester of pregnancy. Prenatal exposure to lead (blood, bone), mercury, and maternal depression were assessed repeatedly and the Toddler Temperament Scale (TTS) was completed when the child was 24 months old. The association between each measure of prenatal exposure and performance on individual TTS subscales was evaluated by multivariable linear regression. Latent profile analysis was used to classify subjects by TTS performance. Multinomial regression models were used to estimate the prospective association between prenatal exposures and TTS performance. RESULTS: 500 mother-child pairs completed the TTS and had complete data on exposures and covariates. Three latent profiles were identified and categorized as predominantly difficult, intermediate, or easy temperament. Prenatal exposure to maternal depression predicted increasing probability of difficult toddler temperament. Maternal bone lead, a marker of cumulative exposure, also predicted difficult temperament. Prenatal lead exposure modified this association, suggesting that joint exposure in pregnancy to both was most toxic. CONCLUSIONS: Maternal depression predicts difficult temperament and concurrent prenatal exposure to maternal depression and lead predicts a more difficult temperament phenotype in 2 year olds. The role of temperament as an intermediate variable in the path from prenatal exposures to neurobehavioral deficits and other health effects deserves further study.