The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80(+)Mac-2(+)) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80(+)Mac-2(neg)), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.

Despite the prominent use of the Suchey-Brooks (S-B) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential interpopulation error rates between geographical locations. This study assessed the accuracy of the S-B method to a contemporary adult population in Queensland, Australia and provides robust age parameters calibrated for our population. Three-dimensional surface reconstructions were generated from computed tomography scans of the pubic symphysis of male and female Caucasian individuals aged 15-70 years (n = 195) in Amira and Rapidform. Error was analyzed on the basis of bias, inaccuracy and percentage correct classification for left and right symphyseal surfaces. Application of transition analysis and Chi-square statistics demonstrated 63.9 and 69.7% correct age classification associated with the left symphyseal surface of Australian males and females, respectively, using the S-B method. Using Bayesian statistics, probability density distributions for each S-B phase were calculated, providing refined age parameters for our population. Mean inaccuracies of 6.77 (±2.76) and 8.28 (±4.41) years were reported for the left surfaces of males and females, respectively; with positive biases for younger individuals (<55 years) and negative biases in older individuals. Significant sexual dimorphism in the application of the S-B method was observed; and asymmetry in phase classification of the pubic symphysis was a frequent phenomenon. These results recommend that the S-B method should be applied with caution in medico-legal death investigations of Queensland skeletal remains and warrant further investigation of reliable age estimation techniques.

Effects of a polyunsaturated fatty acid (PUFA)-rich diet were investigated in 17 polycystic ovary syndrome (PCOS) patients. After a 3-month habitual diet period, dietary fats were partly replaced with PUFAs for another 3 months. The PUFA-rich diet increased plasma linoleic acid from 28.36 +/- 1.00% to 33.76 +/- 1.08% (P < 0.002) and alpha-linolenic acid from 0.52 +/- 0.03% to 1.06 +/- 0.10% (P < 0.0001). Fasting glucose increased from 76 +/- 3 to 95 +/- 3 mg/dl (4.2 +/- 0.2 to 5.30.2 mmol/liter; P < 0.0001), and the area under the curve for glucose during oral glucose tolerance test increased from 421 +/- 34 to 503 +/- 31 mg/dl (23.4 +/- 1.9 to 27.9 +/- 1.7 mmol/liter; P < 0.001). Plasma insulin did not change either at fasting or during oral glucose tolerance test. Fasting plasma free fatty acids decreased from 0.596 +/- 0.048 to 0.445 +/- 0.058 mg/dl (P = 0.037), and ketone bodies decreased from 9.14 +/- 1.57 to 3.63 +/- 0.62 mg/dl (895 +/- 154 to 356 +/- 61 micromol/liter; P < 0.003). Plasma 15-deoxyprostaglandin J(2) tended to decrease (from 239 +/- 65 to 171 +/- 60 ng/ml; P = 0.053). Plasma testosterone, free testosterone, SHBG, dehydroepiandrosterone sulfate, LH, FSH, and urinary estrogen conjugates did not change. Urinary pregnanediol 3-glucuronide increased from 18.6 +/- 2.2 to 31.0 +/- 5.7 micro g/mg creatinine (P = 0.038). In conclusion, increased dietary PUFA intake can exert significant metabolic and endocrine effects in women with PCOS.

Due to disparity regarding the age at which skeletal maturation of the spheno-occipital synchondrosis occurs in forensic and biological literature, this study provides recalibrated multislice computed tomography (MSCT) age standards for the Australian (Queensland) population, using a Bayesian statistical approach. The sample comprises retrospective cranial/cervical MSCT scans obtained from 448 males and 416 females aged birth to 20 years from the Skeletal Biology and Forensic Anthropology Research Osteological Database. Fusion status of the synchondrosis was scored using a modified six-stage scoring tier on an MSCT platform, with negligible observer error (κ = 0.911 ± 0.04, intraclass correlation coefficient = 0.994). Bayesian transition analysis indicates that females are most likely to transition to complete fusion at 13.1 years and males at 15.6 years. Posterior densities were derived for each morphological stage, with complete fusion of the synchondrosis attained in all Queensland males over 16.3 years of age and females aged 13.8 years and older. The results demonstrate significant sexual dimorphism in synchondrosis fusion and are suggestive of intrapopulation variation between major geographic regions in Australia. This study contributes to the growing repository of contemporary anthropological standards calibrated for the Queensland milieu to improve the efficacy of the coronial process for medicolegal death investigation. As a stand-alone age indicator, the basicranial synchondrosis may be consulted as an exclusion criterion when determining the age of majority that constitutes 17 years in Queensland forensic practice.

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