Kinematic difference and asymmetries during level walking in adolescent patients with different types of mild scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), three-dimensional spine deformation, affects body motion. Previous research had indicated pathological gait patterns of AIS. However, the impact of the curve number on the walking mechanism has not been established. Therefore, this study aimed to compare the gait symmetry and kinematics in AIS patients with different curve numbers to healthy control. RESULTS: In the spinal region, double curves AIS patients demonstrated a smaller sagittal symmetry angle (SA) and larger sagittal convex ROM of the trunk and lower spine than the control group. In the lower extremities, the single curve patients showed a significantly reduced SA of the knee joint in the frontal plane, while the double curves patients showed a significantly reduced SA of the hip in the transverse plane. CONCLUSION: The curve number indeed affects gait symmetry and kinematics in AIS patients. The double curves patients seemed to adopt a more "careful walking" strategy to compensate for the effect of spinal deformation on sensory integration deficits. This compensation mainly occurred in the sagittal plane. Compared to double curves patients, single curve patients unitized a similar walking strategy with healthy subjects.

Comparison of plugin and redundant marker sets to analyze gait kinematics between different populations.

BACKGROUND: Gait model consists of a marker set and a segment pose estimation algorithm. Plugin marker set and inverse kinematic algorithm (IK.) are prevalent in gait analysis, especially musculoskeletal motion analysis. Adding extra markers for the plugin marker set could increase the robustness to marker misplacement, motion artifacts, and even markers occlusion. However, how the different marker sets affect the gait analysis's kinematic output is unclear. Therefore, this study aims to investigate the effect of marker sets on the kinematic output during level walking in different populations. RESULTS: In all three planes, there are significant differences (P < 0.05) between marker sets in some kinematic variables at the hip, knee, and ankle. In different populations, the kinematic variables that show significant differences varied. When comparing the kinematic differences between populations using the two marker sets separately, the range of motion (ROM) of hip flexion was only found to be a significant difference using the redundant marker set, while the peak internal rotation at the knee was only found a significant difference using plugin marker set. In addition, the redundant marker set shows less intra-subject variation than the plugin marker set. CONCLUSION: The findings in this study demonstrate the importance of marker set selection since it could change the result when comparing the kinematic differences between populations. Therefore, it is essential to increase the caution in explaining the result when using different marker sets. It is crucial to use the same marker set, and the redundant marker set might be a better choice for gait analysis.

Cranial Bone Transport Promotes Angiogenesis, Neurogenesis, and Modulates Meningeal Lymphatic Function in Middle Cerebral Artery Occlusion Rats.

BACKGROUND: Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model. METHODS: CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function. RESULTS: CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats. CONCLUSIONS: This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1-4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non-AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid-etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone-like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC-Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy-dispersive X-ray spectroscopy analysis demonstrated a lower calcium-to-phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno-canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS.-Chen, H., Zhang, J., Wang, Y., Cheuk, K.-Y., Hung, A. L. H., Lam, T.-P., Qiu, Y., Feng, J. Q., Lee, W. Y. W., Cheng, J. C. Y. Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis.

Lgr5-overexpressing mesenchymal stem cells augment fracture healing through regulation of Wnt/ERK signaling pathways and mitochondrial dynamics.

Fracture remains one of the most common traumatic conditions in orthopedic surgery. The use of mesenchymal stem cells (MSCs) to augment fracture repair is promising. Leucine-rich repeat-containing GPCR 5 (Lgr5), a transmembrane protein, has been identified as a novel adult stem cell marker in various organs and tissues. However, the roles of Lgr5 in MSCs are not fully understood. In this study, we investigated cellular functions of Lgr5 in MSCs and its potential implications in treating fracture. Lgr5-overexpressing MSCs (MSCLgr5) were established in murine SV40 promoter-driven luciferase reporter MSC line through virus transfection. Results of real-time quantitative PCR and Western blot analysis confirmed the increased expression of Lgr5 in MSCLgr5. MSCLgr5 exhibited increased osteogenic capacity, which may result from elevated expression of ß-catenin and phosphorylated ERK1/2 within the nuclear region of cells. In contrast, inhibition of Lgr5 expression decreased the osteogenic differentiation ability of MSCs, accompanied with increased mitochondrial fragmentation and reduced expression of ß-catenin. Local transplantation of MSCLgr5 at fracture sites accelerated fracture healing via enhanced osteogenesis and angiogenesis. MSCLgr5 stimulated the tube formation capacity of HUVECs in a Matrigel coculture system in vitro significantly. Taken together, results suggest that Lgr5 is implicated in the cellular processes of osteogenic differentiation of MSCs through regulation of Wnt and ERK signaling pathways and mitochondrial dynamics in fusion and fission. Inhibition of Lgr5 expression induced increased mitochondrial fragmentation and suppression of osteogenesis. MSCLgr5 exhibited enhanced therapeutic efficacy for fracture healing, which may serve as a superior cell source for bone tissue repair.-Lin, W., Xu, L., Pan, Q., Lin, S., Feng, L., Wang, B., Chen, S., Li, Y., Wang, H., Li, Y., Wang, Y., Lee, W. Y. W., Sun, D., Li, G. Lgr5-overexpressing mesenchymal stem cells augment fracture healing through regulation of Wnt/ERK signaling pathways and mitochondrial dynamics.

Volumetric assessment of unaffected parenchyma and Wilms' tumours: analysis of response to chemotherapy and surgery using a semi-automated segmentation algorithm in children with renal neoplasms.

OBJECTIVE: To present our proof of concept with semi-automatic image recognition/segmentation technology for calculation of tumour/parenchyma volume. METHODS: We reviewed Wilms' tumours (WTs) between 2000 and 2018, capturing computed tomography images at baseline, after neoadjuvant chemotherapy (NaC) and postoperatively. Images were uploaded into MATLAB-3-D volumetric image processing software. The program was trained by two clinicians who supervised the demarcation of tumour and parenchyma, followed by automatic recognition and delineation of tumour margins on serial imaging, and differentiation from uninvolved renal parenchyma. Volume was automatically calculated for both. RESULTS: During the study period, 98 patients were identified. Of these, based on image quality and availability, 32 (38 affected moieties) were selected. Most patients (65%) were girls, diagnosed at age 50 ± 37 months of age. NaC was employed in 64% of patients. Surgical management included 27 radical and 11 partial nephrectomies. Automated volume assessment demonstrated objective response to NaC for unilateral and bilateral tumours (68 ± 20% and 53 ± 39%, respectively), as well as preservation on uninvolved parenchyma with partial nephrectomy (70 ± 46 cm3 at presentation to 57 ± 41 cm3 post-surgery). CONCLUSION: Volumetric analysis is feasible and allows objective assessment of tumour and parenchyma volume in response to chemotherapy and surgery. Our data show changes after therapy that may be otherwise difficult to quantify. Use of such technology may improve surgical planning and quantification of response to treatment, as well as serving as a tool to predict renal reserve and long-term changes in renal function.

Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and ß-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active ß-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/ß-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Characterization of Autism Spectrum Disorder across the Age Span by Intrinsic Network Patterns.

Autism spectrum disorder (ASD) is characterized by abnormal functional organization of brain networks, which may underlie the cognitive and social impairments observed in affected individuals. The present study characterizes unique intrinsic connectivity within- and between- neural networks in children through to adults with ASD, relative to controls. Resting state fMRI data were analyzed in 204 subjects, 102 with ASD and 102 age- and sex-matched controls (ages 7-40 years), acquired on a single scanner. ASD was assessed using the autism diagnostic observation schedule (ADOS). BOLD correlations were calculated between 47 regions of interest, spanning seven resting state brain networks. Partial least squares (PLS) analyses evaluated the association between connectivity patterns and ASD diagnosis as well as ASD severity scores. PLS demonstrated dissociable connectivity patterns in those with ASD, relative to controls. Similar patterns were observed in the whole cohort and in a subgroup analysis of subjects under 18 years of age. Greater inter-network connectivity was seen in ASD with greater intra-network connectivity in controls. In conclusion, stronger inter-network and weaker intra-network resting state-fMRI BOLD correlations characterize ASD and may differentiate control and ASD cohorts. These findings are relevant to understanding ASD as a disruption of network topology.

Natural Killer Cell-Based Cancer Immunotherapy: A Review on 10 Years Completed Clinical Trials.

NK cell cancer immunotherapy is an emerging anti-tumour therapeutic strategy that explores NK cell stimulation. In this review, we address strategies developed to circumvent limitations to clinical application of NK cell-based therapies, and comprehensively review the design and results of clinical trials conducted in the past 10 years (2008-2018) to test their therapeutic potential. NK cell-based immunotherapy of solid cancers remains controversial, but merit further detailed investigation.

Longitudinal Study of White Matter Development and Outcomes in Children Born Very Preterm.

Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions.

Magnetic resonance thermometry of flowing blood.

Blood temperature is a key determinant of tissue temperature and can be altered under normal physiological states, such as exercise, in diseases such as stroke or iatrogenically in therapies which modulate tissue temperature, such as therapeutic hypothermia. Currently available methods for the measurement of arterial and venous temperatures are invasive and, for small animal models, are impractical. Here, we present a methodology for the measurement of intravascular and tissue temperature by magnetic resonance imaging (MRI) using the lanthanide agent TmDOTMA- (DOTMA, tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Tm, thulium). The approach makes use of phase-sensitive imaging measurements, combined with spectrally selective excitation, to monitor the temperature-dependent shift in the resonance of proton nuclei associated with water and with methyl groups of TmDOTMA- . Measurements were first made in a flow phantom modelling diastolic blood flow in the mouse aorta or inferior vena cava (IVC) and imaged using 7-T preclinical MRI with a custom-built surface coil. Flowing and static fluid temperatures agreed to within 0.12°C for these experiments. Proof-of-concept experiments were also performed on three healthy adult mice, demonstrating temperature measurements in the aorta, IVC and kidney following a bolus injection of contrast agent. A small (0.7-1°C), but statistically significant, higher kidney temperature compared with the aorta (p = 0.002-0.007) and IVC (p = 0.003-0.03) was shown in all animals. These findings demonstrate the feasibility of the technique for in vivo applications and illustrate how the technique could be used to explore the relationship between blood and tissue temperature for a wide range of applications.

B1 mapping for bias-correction in quantitative T1 imaging of the brain at 3T using standard pulse sequences.

PURPOSE: B1 mapping is important for many quantitative imaging protocols, particularly those that include whole-brain T1 mapping using the variable flip angle (VFA) technique. However, B1 mapping sequences are not typically available on many magnetic resonance imaging (MRI) scanners. The aim of this work was to demonstrate that B1 mapping implemented using standard scanner product pulse sequences can produce B1 (and VFA T1 ) maps comparable in quality and acquisition time to advanced techniques. MATERIALS AND METHODS: Six healthy subjects were scanned at 3.0T. An interleaved multislice spin-echo echo planar imaging double-angle (EPI-DA) B1 mapping protocol, using a standard product pulse sequence, was compared to two alternative methods (actual flip angle imaging, AFI, and Bloch-Siegert shift, BS). Single-slice spin-echo DA B1 maps were used as a reference for comparison (Ref. DA). VFA flip angles were scaled using each B1 map prior to fitting T1 ; the nominal flip angle case was also compared. RESULTS: The pooled-subject voxelwise correlation (ρ) for B1 maps (BS/AFI/EPI-DA) relative to the reference B1 scan (Ref. DA) were ρ = 0.92/0.95/0.98. VFA T1 correlations using these maps were ρ = 0.86/0.88/0.96, much better than without B1 correction (ρ = 0.53). The relative error for each B1 map (BS/AFI/EPI-DA/Nominal) had 95th percentiles of 5/4/3/13%. CONCLUSION: Our findings show that B1 mapping implemented using product pulse sequences can provide excellent quality B1 (and VFA T1 ) maps, comparable to other custom techniques. This fast whole-brain measurement (∼2 min) can serve as an excellent alternative for researchers without access to advanced B1 pulse sequences. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1673-1682.

Defining the bone morphometry, micro-architecture and volumetric density profile in osteopenic vs non-osteopenic adolescent idiopathic scoliosis.

PURPOSE: Osteopenia has been widely reported in about 30 % of girls with adolescent idiopathic scoliosis (AIS). However, the bone quality profile of the 70 % non-osteopenic AIS defined by areal bone mineral density (BMD) with conventional dual-energy X-ray absorptiometry (DXA) has not been adequately studied. Our purpose was to verify whether abnormal volumetric BMD (vBMD) and bone structure (morphometry and micro-architecture) also existed in the non-osteopenic AIS when compared with matched controls using both DXA and high-resolution peripheral computed tomography (HR-pQCT). METHODS: This was a case-control cross-sectional study. 257 AIS girls with a mean age of 12.7 (SD = 0.8) years old and 187 age- and gender-matched normal controls with an average age of 12.9 (SD = 0.5) years old were included. Areal BMD (aBMD) and bone quality were measured with standard DXA and HR-pQCT, respectively. The parameters of HR-pQCT could be categorized as bone morphometry, vBMD and bone micro-architecture. The results were compared between the osteopenic AIS and osteopenic control, and between the non-osteopenic AIS and non-osteopenic control. RESULTS: In addition to the lower aBMD and vBMD, osteopenic AIS showed significantly greater cortical perimeter and trabecular area than the osteopenic control even after adjustments of age (P < 0.05). Non-osteopenic AIS also showed significantly lower aBMD together with lower cortical area, thickness and vBMD than the non-osteopenic control (P < 0.05). After adjustments of age, cortical area and vBMD, and trabecular number and separation continued to show statistical significance (P < 0.05). Both the osteopenic and non-osteopenic AIS subgroups revealed significant abnormal bone quality parameters from that in the control group after adjustments of age and aBMD with multi-linear regression analysis (P < 0.05). CONCLUSIONS: The present study specifically defined the abnormal profile of bone quality in the osteopenic and non-osteopenic AIS for the first time. Both the osteopenic and non-osteopenic AIS were likely to have relatively lower bone mineral status and abnormal bone morphometry, micro-architecture and volumetric density profile compared with their normal matched controls. The observed abnormalities were suggestive of decreased endocortical bone apposition or active endocortical resorption that could affect the mechanical bone strength in AIS. The underlying pathomechanism might be attributed to abnormal bone modeling/remodeling that could be associated with the etiopathogenesis of AIS.

Oxidized Regenerated Cellulose/Collagen Dressings: Review of Evidence and Recommendations.

OBJECTIVE: Healthcare systems are being challenged to manage increasing numbers of nonhealing wounds. Wound dressings are one of the first lines of defense in wound management, and numerous options exist. The oxidized regenerated cellulose (ORC)/collagen dressing may offer healthcare providers a robust and cost-effective tool for use in a variety of wounds. DESIGN: A multidisciplinary panel meeting was convened to discuss the use of ORC/collagen dressings in wound care and provide practice recommendations. A literature search was conducted to provide a brief review of the peer-reviewed studies published between January 2000 and March 2016 to inform the meeting. SETTING: A 2-day panel meeting convened in February 2017. PARTICIPANTS: Healthcare providers with experience using ORC/collagen dressings. This multidisciplinary panel of 15 experts in wound healing included podiatrists, wound care specialists (doctors, certified wound care nurses, and research scientists), and an orthopedist. RESULTS: The literature search identified 58 articles, a majority of which were low levels of evidence (69.3% were level 3 or lower). Panel members identified wound types, such as abrasions, burns, stalled wounds, diabetic foot ulcers, and pressure injuries, where ORC/collagen dressing use could be beneficial. Panel members then provided recommendations and technical pearls for the use of ORC/collagen dressings in practice. Barriers to ORC/collagen dressing use were discussed, and potential resolutions were offered. CONCLUSIONS: An ORC/collagen dressing can be a critical tool for clinicians to help manage a variety of wounds. Clinical and economic studies comparing standard-of-care dressings and plain collagen dressings to ORC/collagen dressings are needed.

Atypical functional brain connectivity during rest in autism spectrum disorders.

OBJECTIVE: Connectivity atypicalities in autism spectrum disorders (ASD) have been extensively proposed. The default mode network (DMN) is critical in this study, given the insight it provides for long-distance connectivity, and the importance of regions in this network for introspection and social emotion processing, areas affected in ASD. However, study of this network has largely been limited to adults; research earlier in development is lacking. The objective of this study was to examine DMN connectivity in children/adolescents with ASD. METHODS: A total of 115 children/adolescents, aged 6 to 17 years (71 males with ASD and 44 group age-matched TD males) were included in these analyses. We examined group differences in (1) functional connectivity between the posterior cingulate cortex and regions across the brain, (2) connectivity within the DMN as a function of age and intelligence quotient (IQ), and (3) the association between DMN connectivity and empathic accuracy. RESULTS: Individuals with ASD, relative to controls, showed either stronger or weaker connectivity between the posterior cingulate cortex (PCC) and DMN regions, depending on the region, but also showed stronger connectivity with non-DMN regions. A significant group-by-age interaction was observed in functional connectivity between the PCC and medial prefrontal cortex; connectivity increased with age in controls, but decreased in individuals with ASD. No effects of IQ were found. There was a significant group difference in the relation between DMN connectivity and empathic accuracy. INTERPRETATION: Differences in functional connectivity may suggest the presence of neural atypicalities that impact the development of typical connectivity in ASD. In addition to affecting DMN dynamics, these atypicalities may also impact social-cognitive abilities.

Effects of Sclerostin Antibody on the Healing of Femoral Fractures in Ovariectomised Rats.

The inhibition of sclerostin by the systemic administration of a monoclonal antibody (Scl-Ab) significantly increased bone mass and strength in fractured bones in animal models and non-fractured bones in ovariectomised (OVX) rats. In this study, the effects of Scl-Ab on healing were examined in a closed fracture model in OVX rats. Sixty Sprague-Dawley rats underwent an ovariectomy or a sham operation at 4 months of age, and a closed fracture of the right femur was performed 3 months later. Subcutaneous injections with Scl-Ab (25 mg/kg) or saline were then administered on day 1 after the fracture and twice a week for 8 weeks (n = 20 per group), at which time the fractured femurs were harvested for micro-computed tomography analysis, four-point bending mechanical testing and histomorphometric analysis to examine bone mass, bone strength and dynamic bone formation at the fracture site. The angiogenesis at the fracture site was also examined. Bone marrow stem cells were also isolated from the fractured bone to perform a colony-forming unit (CFU) assay and an alkaline phosphatase-positive (ALP(+)) CFU assay. OVX rats treated with Scl-Ab for 8 weeks had significantly increased bone mineral density and relative bone volume compared with OVX rats treated with saline. Similarly, maximum loading, energy to maximum load and stiffness in Scl-Ab-treated OVX rats were significantly higher than those in saline controls. The mineral apposition rate (MAR), mineralising surface (MS/BS) and bone formation rate (BFR/BS) were also significantly increased in Scl-Ab-treated group compared with the saline-treated group in OVX rats. Furthermore, the Scl-Ab-treated group had more CFUs and ALP(+) CFUs than the saline-treated group in OVX rats. No significant difference in angiogenesis at the fracture site was found between the groups. Our study demonstrated that Scl-Ab helped to increase bone mass, bone strength and bone formation at the fracture site in a closed femoral fracture model in OVX rats. Bone marrow stem cells in OVX rats injected with Scl-Ab also had increased CFUs and ALP(+) CFUs.

Longitudinal cerebellar growth following very preterm birth.

PURPOSE: To measure cerebellar growth in a longitudinal cohort of very preterm infants to identify early predictors of subsequent brain growth. Although the cerebellum grows rapidly during late gestation, the rate and variability of growth following premature birth, and the effects of associated injury, are largely unknown. MATERIALS AND METHODS: In all, 105 very-preterm born infants (24-32 weeks GA) were imaged using magnetic resonance imaging (MRI) at birth, term-equivalent, 2, and 4 years of age. Cerebellar and total cerebral volumes were estimated from 1 mm isotropic T1 -weighted scans acquired at 1.5T and 3T, using an atlas-based approach. Linear models were used to analyze cerebellar volume as cross-sectional and longitudinal functions of age, clinical, and radiological correlates. Linear models were also used to test for associations between volume and cognitive outcome. RESULTS: Cerebellar volume increased rapidly with age-at-scan during both the preterm (0.7 mL/wk, P < 0.001) and term periods (1.8 mL/wk, P < 0.001). Infants with grade 3 or 4 germinal matrix hemorrhage (GMH) had smaller cerebellar volumes as a percentage of total brain volume starting at birth and continuing to 4 years of age (-0.43%, -0.57%, -1.09% at preterm, term, and 4 years, respectively, P < 0.01). Irrespective of age-at-scan, early cerebellar volume was predictive of volume at 4 years of age (slope = 1.3, P < 0.001). Cerebellar volumes were not found to predict cognitive outcome at 4 years of age; P < 0.2. CONCLUSION: High-grade GMH and small perinatal cerebellar size is predictive of cerebellar development up to 4 years of age. These findings suggest that it is possible to identify individuals at high risk of reduced cerebellar volumes at an early age. J. Magn. Reson. Imaging 2016;43:1462-1473.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.