Brain templates for Chinese babies from newborn to three months of age.

The infant brain develops rapidly and this area of research has great clinical implications. Neurodevelopmental disorders such as autism and developmental delay have their origins, potentially, in abnormal early brain maturation. Searching for potential early neural markers requires a priori knowledge about infant brain development and anatomy. One of the most common methods of characterizing brain features requires normalization of individual images into a standard stereotactic space and conduct of group-based analyses in this space. A population representative brain template is critical for these population-based studies. Little research is available on constructing brain templates for typical developing Chinese infants. In the present work, a total of 120 babies from 5 to 89 days of age were included with high resolution structural magnetic resonance imaging scans. T1-weighted and T2-weighted templates were constructed using an unbiased registration approach for babies from newborn to 3 months of age. Age-specific templates were also estimated for babies aged at 0, 1, 2 and 3 months old. Then we conducted a series of evaluations and statistical analyses over whole tissue segmentations and brain parcellations. Compared to the use of population mismatched templates, using our established templates resulted in lower deformation energy to transform individual images into the template space and produced a smaller registration error, i.e., smaller standard deviation of the registered images. Significant volumetric growth was observed across total brain tissues and most of the brain regions within the first three months of age. The total brain tissues exhibited larger volumes in baby boys compared to baby girls. To the best of our knowledge, this is the first study focusing on the construction of Chinese infant brain templates. These templates can be used for investigating birth related conditions such as preterm birth, detecting neural biomarkers for neurological and neurodevelopmental disorders in Chinese populations, and exploring genetic and cultural effects on the brain.

Epidemiologic Changes of Neonatal Early-onset Sepsis After the Implementation of Universal Maternal Screening for Group B Streptococcus in Hong Kong.

BACKGROUND: The epidemiology of neonatal early-onset sepsis (EOS) has changed with time and with changes in prevention strategy. Population-representative contemporary data provide insights on how to further improve EOS prevention and triage strategies. METHODS: Neonates born in public hospitals in Hong Kong from January 1, 2006, to December 31, 2017 were included. The epidemiological characteristics of EOS and the use of intrapartum antibiotic prophylaxis (IAP) were compared between the 2 epochs before (January 1, 2006 to December 31, 2011) and after (January 1, 2012 to December 31, 2017) the territory-wide implementation of universal maternal group B Streptococcus (GBS) screening. RESULTS: EOS developed in 1.07‰ of live births (522/490,034). After the implementation of universal GBS screening, the EOS rate decreased in neonates born ≥34 weeks (1.17‰-0.56‰, P < 0.001) and remained similar in those born <34 weeks (7.8‰-10.9‰, P = 0.15), whereas the proportions of IAP coverage increased in both groups [7.6%-23.3% ( P < 0.001) and 28.5%-52.0% ( P < 0.001), respectively]. The major pathogen for EOS shifted from GBS to Escherichia coli , and for early-onset meningitis from GBS to Streptococcus bovis . IAP was associated with subsequent isolation of pathogens resistant to ampicillin [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI): 1.3-4.2], and second-generation [aOR 2.0; 95% CI: 1.02-4.3] and third-generation [aOR 2.2; 95% CI: 1.1-5.0] cephalosporins. CONCLUSIONS: Pathogen profile of EOS changed with the implementation of universal GBS screening. S. bovis has emerged as a more common pathogen associated with the risk of meningitis. IAP may not be as effective in reducing EOS rate among infants born <34 weeks as compared with those ≥34 weeks, and newer strategies may be needed.

Deficits in neural encoding of speech in preterm infants.

Preterm children show developmental cognitive and language deficits that can be subtle and sometimes undetectable until later in life. Studies of brain development in children who are born preterm have largely focused on vascular and gross anatomical characteristics rather than pathophysiological processes that may contribute to these developmental deficits. Neural encoding of speech as reflected in EEG recordings is predictive of future language development and could provide insights into those pathophysiological processes. We recorded EEG from 45 preterm (≤ 34 weeks of gestation) and 45 term (≥ 38 weeks) Chinese-learning infants 0-12 months of (corrected) age during natural sleep. Each child listened to three speech stimuli that differed in lexically meaningful pitch (2 native and 1 non-native speech categories). EEG measures associated with synchronization and gross power of the frequency following response (FFR) were examined. ANCOVAs revealed no main effect of stimulus nativeness but main effects of age, consistent with earlier studies. A main effect of prematurity also emerged, with synchronization measures showing stronger group differences than power. By detailing differences in FFR measures related to synchronization and power, this study brings us closer to identifying the pathophysiological pathway to often subtle language problems experienced by preterm children.

Secular trends of sleep-wake patterns in Hong Kong preschoolers.

OBJECTIVE: To evaluate the secular trends of sleep-wake patterns of Hong Kong preschool children. METHODS: Kindergartens from the four geographical regions of Hong Kong were randomly invited to take part in a sleep survey in 2012 and again in 2018. The parent-completed questionnaire provided information on socioeconomic status (SES), children's, and parental sleep-wake patterns. Secular trends and risk factors associated with short sleep duration in preschoolers were explored. RESULTS: A sample of 5048 preschool children was included in the secular comparison, with 2306 and 2742 from the 2012 and 2018 surveys, respectively. A higher percentage of children in 2018 (41.1% vs 26.7%, p < 0.001) did not achieve the recommended sleep duration. During the survey years, sleep duration decreased by 13 ([95%CI: 18.5 to -8.1]) and 18 min ([95%CI: 23.6 to -12.2]) on weekdays and weekends, respectively. The overall trend of nap decrease was not significant. Sleep onset latency significantly increased on both weekdays (6 min [95%CI: 3.5 to 8.5]) and weekends (7 min [95%CI: 4.7 to 9.9]). Children's sleep duration was positively correlated with parental sleep duration with a correlation coefficient ranging from 0.16 to 0.27 (p < 0.001). CONCLUSIONS: A significant proportion of Hong Kong preschool children did not achieve the recommended amount of sleep. A downward secular trend in sleep duration was observed during the survey period. Public health measures to improve sleep duration in preschool children should be a high priority.

Nebulization of siRNA for inhalation therapy based on a microfluidic surface acoustic wave platform.

The local delivery of therapeutic small interfering RNA or siRNA to the lungs has the potential to improve the prognosis for patients suffering debilitating lung diseases. Recent advances in materials science have been aimed at addressing delivery challenges including biodistribution, bioavailability and cell internalization, but an equally important challenge to overcome is the development of an inhalation device that can deliver the siRNA effectively to the lung, without degrading the therapeutic itself. Here, we report the nebulization of siRNA, either naked siRNA or complexed with polyethyleneimine (PEI) or a commercial transfection agent, using a miniaturizable acoustomicrofluidic nebulization device. The siRNA solution could be nebulised without significant degradation into an aerosol mist with tunable mean aerodynamic diameters of approximately 3 µm, which is appropriate for deep lung deposition via inhalation. The nebulized siRNA was tested for its stability, as well as its toxicity and gene silencing properties using the mammalian lung carcinoma cell line A549, which demonstrated that the gene silencing capability of siRNA is retained after nebulization. This highlights the potential application of the acoustomicrofluidic device for the delivery of efficacious siRNA via inhalation, either for systemic delivery via the alveolar epithelium or local therapeutic delivery to the lung.

Early Development of Neural Speech Encoding Depends on Age but Not Native Language Status: Evidence From Lexical Tone.

We investigated the development of early-latency and long-latency brain responses to native and non-native speech to shed light on the neurophysiological underpinnings of perceptual narrowing and early language development. Specifically, we postulated a two-level process to explain the decrease in sensitivity to non-native phonemes toward the end of infancy. Neurons at the earlier stages of the ascending auditory pathway mature rapidly during infancy facilitating the encoding of both native and non-native sounds. This growth enables neurons at the later stages of the auditory pathway to assign phonological status to speech according to the infant's native language environment. To test this hypothesis, we collected early-latency and long-latency neural responses to native and non-native lexical tones from 85 Cantonese-learning children aged between 23 days and 24 months, 16 days. As expected, a broad range of presumably subcortical early-latency neural encoding measures grew rapidly and substantially during the first two years for both native and non-native tones. By contrast, long-latency cortical electrophysiological changes occurred on a much slower scale and showed sensitivity to nativeness at around six months. Our study provided a comprehensive understanding of early language development by revealing the complementary roles of earlier and later stages of speech processing in the developing brain.

Neural Speech Encoding in Infancy Predicts Future Language and Communication Difficulties.

Purpose This study aimed to construct an objective and cost-effective prognostic tool to forecast the future language and communication abilities of individual infants. Method Speech-evoked electroencephalography (EEG) data were collected from 118 infants during the first year of life during the exposure to speech stimuli that differed principally in fundamental frequency. Language and communication outcomes, namely four subtests of the MacArthur-Bates Communicative Development Inventories (MCDI)-Chinese version, were collected between 3 and 16 months after initial EEG testing. In the two-way classification, children were classified into those with future MCDI scores below the 25th percentile for their age group and those above the same percentile, while the three-way classification classified them into < 25th, 25th-75th, and > 75th percentile groups. Machine learning (support vector machine classification) with cross validation was used for model construction. Statistical significance was assessed. Results Across the four MCDI measures of early gestures, later gestures, vocabulary comprehension, and vocabulary production, the areas under the receiver-operating characteristic curve of the predictive models were respectively .92 ± .031, .91 ± .028, .90 ± .035, and .89 ± .039 for the two-way classification, and .88 ± .041, .89 ± .033, .85 ± .047, and .85 ± .050 for the three-way classification (p < .01 for all models). Conclusions Future language and communication variability can be predicted by an objective EEG method that indicates the function of the auditory neural pathway foundational to spoken language development, with precision sufficient for individual predictions. Longer-term research is needed to assess predictability of categorical diagnostic status. Supplemental Material https://doi.org/10.23641/asha.15138546.

Prenatal methylmercury exposure is associated with decrease heart rate variability in children.

BACKGROUND: Although several epidemiological studies have suggested mercury (Hg) might be associated with cardiotoxicity, the impact of Hg exposure on cardiac autonomic activity and blood pressure in children has not been investigated at Hg exposure levels equivalent to the Environmental Protection Agency (EPA) reference dose. OBJECTIVE: To investigate the association between low dose prenatal and recent methylmercury (MeHg) exposures and cardiac autonomic function and blood pressure with adjustment for factors such as fish consumption among children from a high fish consumption coastal city. METHODS: Children aged 7-8 years were recruited from the birth cohort of our previous study. Heart rate variability (HRV), resting heart rate (RHR) and blood pressure were measured as surrogate markers of cardiac autonomic function. Cord blood and current whole blood Hg concentration were used as biomarkers of prenatal and recent MeHg exposure, respectively. Recent fish consumption information was estimated with a food frequency questionnaire. RESULTS: Among 604 children, median cord blood and whole blood Hg concentrations were 45.9 nmol/L (IQR: 32.8-65.03 nmol/L) and 13.57 nmol/L (IQR: 9.29-19.72 nmol/L), respectively. Our results demonstrated that prenatal MeHg exposure was associated with decreased HRV (i.e. low CVRR, SDRR, and RMSSD), reflecting reduced parasympathetic activity (i.e. low CCVHF and HF), and a sympathovagal balance shift toward sympathetic predominance (i.e. high %LF and LF/HF ratio). Adjustment of recent fish consumption further increased the significance and magnitude of the adverse associations of MeHg. CONCLUSION: The results of this study suggest that prenatal MeHg exposure is associated with decreased parasympathetic modulation of cardiac autonomic function in children.

Enhanced Neural Differentiation Using Simultaneous Application of 3D Scaffold Culture, Fluid Flow, and Electrical Stimulation in Bioreactors.

Neural differentiation is studied using a simultaneous application of 3D scaffold culture and hydrodynamic and electrical stimuli in purpose-designed recirculation bioreactors operated with continuous fluid flow. Pheochromocytoma (PC12) cells are seeded into nonwoven microfibrous viscose-rayon scaffolds functionalized with poly-l-lysine and laminin. Compared with the results from static control cultures with and without electrical stimulation and bioreactor cultures with the fluid flow without electrical stimulation, expression levels of the differentiation markers ß3-tubulin, shootin1, and ephrin type-A receptor 2 are greatest when cells are cultured in bioreactors with fluid flow combined with in-situ electrical stimulus. Immunocytochemical assessment of neurite development and morphology within the scaffolds confirm the beneficial effects of exposing the cells to concurrent hydrodynamic and electrical treatments. Under the conditions tested, electrical stimulation by itself produces more pronounced levels of cell differentiation than fluid flow alone; however, significant additional improvements in differentiation are achieved by combining these treatments. Fluid flow and electrical stimuli exert independent and noninteractive effects on cellular differentiation, suggesting that interference between the mechanisms of differentiation enhancement by these two treatments is minimal during their simultaneous application. This work demonstrates the beneficial effects of combining several different potent physical environmental stimuli in cell culture systems to promote neurogenesis.

Label-Free Isolation and Single Cell Biophysical Phenotyping Analysis of Primary Cardiomyocytes Using Inertial Microfluidics.

To advance the understanding of cardiomyocyte (CM) identity and function, appropriate tools to isolate pure primary CMs are needed. A label-free method to purify viable CMs from mouse neonatal hearts is developed using a simple particle size-based inertial microfluidics biochip achieving purities of over 90%. Purified CMs are viable and retained their identity and function as depicted by the expression of cardiac-specific markers and contractility. The physico-mechanical properties of sorted cells are evaluated using downstream real-time deformability cytometry. CMs exhibited different physico-mechanical properties when compared with non-CMs. Taken together, this CM isolation and phenotyping method could serve as a valuable tool to progress the understanding of CM identity and function, and ultimately benefit cell therapy and diagnostic applications.

Association between genetic variations in GSH-related and MT genes and low-dose methylmercury exposure in children and women of childbearing age: a pilot study.

BACKGROUND: Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics. OBJECTIVE: To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age. METHODS: A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses. RESULTS: The presence of minor alleles of GCLC-129 (rs17883901), GPX1-198 (rs1050450) and MT1M (rs9936741) were associated with significantly lower hair tHg levels in mothers whereas mothers with minor alleles of GSTP1-105(rs1695) and MT1M (rs2270836) have significantly higher hair tHg levels. After adjustment for fish consumption and other confounding factors, apart from MT1M (rs2270836), all of the above SNPs remain significant in the multivariable linear regression models. CONCLUSIONS: Our results in a group of children and women show that genetic variants of GSH-related and MT genes are associated with hair Hg concentrations. These genetic variations are likely to significantly affect MeHg metabolism and thus influence the accumulation of Hg in the human body.

Fast three-dimensional micropatterning of PC12 cells in rapidly crosslinked hydrogel scaffolds using ultrasonic standing waves.

The ability to spatially organise the microenvironment of tissue scaffolds unlocks the potential of many scaffold-based tissue engineering applications. An example application is to aid the regeneration process of peripheral nerve injuries. Herein, we present a promising approach for three-dimensional (3D) micropatterning of nerve cells in tissue scaffolds for peripheral nerve repair. In particular, we demonstrate the 3D micropatterning of PC12 cells in a gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogel using ultrasound standing waves (USWs). PC12 cells were first aligned in 3D along nodal planes by the USWs in Gtn-HPA hydrogel precursor solution. The precursor was then crosslinked using horseradish peroxidase (HRP) and diluted hydrogen peroxide (H2O2), thus immobilising the aligned cells within 90-120 s. This micropatterning process is cost effective and can be replicated easily without the need for complex and expensive specialised equipment. USW-aligned PC12 cells showed no adverse effect in terms of viability or ability to proliferate. To our best knowledge, this is the first report on the effect of USW alignment on neural cell differentiation. Differentiated and USW-aligned PC12 cells showed directional uniformity after 20 d, making this technique a promising alternative approach to guide the nerve regeneration process.

Electrical stimulation of cell growth and neurogenesis using conductive and nonconductive microfibrous scaffolds.

The effect of exogenous electrical stimulation on cell viability, attachment, growth, and neurogenesis was examined using PC12 cells in microfibrous viscose-rayon scaffolds immersed in culture medium. The scaffolds were applied either in their nonconductive state or after coating the fibres with 200 nm of gold to give a scaffold sheet resistivity of (13 ± 1.3) Ω square-1. The cells were treated for 12 days using direct current electrical stimulation of 2 h per day. No cytotoxic effects were observed when up to 500 mV (8.3 mV mm-1) was applied to the scaffolds without gold, or when up to 100 mV (1.7 mV mm-1) was applied to the scaffolds with gold. Compared with unstimulated cells, whereas electrical stimulation significantly enhanced cell growth and attachment in the nonconductive scaffolds without gold, similar effects were not found for the conductive scaffolds with gold. Neural differentiation in the presence of nerve growth factor was improved by electrical stimulation in both scaffolds; however, neurite development and the expression of key differentiation markers were greater in the nonconductive scaffolds without gold than in the scaffolds with gold. Application of the same current to scaffolds with and without gold led to much higher levels of neurogenesis in the scaffolds without gold. This work demonstrates that substantial benefits in terms of cell growth and neural differentiation can be obtained using electric fields exerted across nonconductive microfibrous scaffolds, and that this approach to electrical stimulation can be more effective than when the stimulus is applied to cells on conductive scaffolds.

Printing in situ tissue sealant with visible-light-crosslinked porous hydrogel.

To reflect the rapidly growing interest in producing tissue sealants using various chemical/physical processes, we report an approach using visible light to control the crosslinking of 3D printable hydrogels as in situ tissue sealant. Gelatin-hydroxyphenylpropionic acid conjugate (Gtn-HPA) is shown to crosslink effectively within 30 s under visible light in the presence of [RuII(bpy)3]2+ and sodium persulphate, which is sufficiently rapid for surgery use. Porous structure can be also introduced by including carboxylmethyl cellulose-tyramine (CMC-Tyr) as a precursor. The detailed parameters involved in the hydrogel formation, including irradiation time and distance, are investigated in this study. The results suggested that a longer exposure time would result in a hydrogel with higher crosslinking density, while sufficient photocrosslinking can be achieved using a routine visible light source at a distance of 100 mm. Surface morphology of the photocrosslinked hydrogels are studied using scanning electron microscopy (SEM) and environmental SEM with results confirming the expected porosity. The tensile strength of the photocrosslinked hydrogels has been tested for both non-porous and porous samples. Notably, the adhesive strengths (adhesion) of the photocrosslinked hydrogels was demonstrated to be significantly higher compared to that of commercial fibrin glue. Finally, a prototype of hand-held applicator has been developed and demonstrated to print out Gtn-HPA/CMC-Tyr hydrogel of designed properties with controlled spatial resolution. The development of both material and applicator in this study provides a promising tissue sealant solution for wound closure in future surgical procedures.

Microparticle Delivery of Protein Markers for Single-Cell Western Blotting from Microwells.

Immunoblotting confers protein identification specificity beyond that of immunoassays by prepending protein electrophoresis (sizing) to immunoprobing. To accurately size protein targets, sample analysis includes concurrent analysis of protein markers with known molecular masses. To incorporate protein markers in single-cell western blotting, microwells are used to isolate individual cells and protein marker-coated microparticles. A magnetic field directs protein-coated microparticles to >75% of microwells, so as to 1) deliver a quantum of protein marker to each cell-laden microwell and 2) synchronize protein marker solubilization with cell lysis. Nickel-coated microparticles are designed, fabricated, and characterized, each conjugated with a mixture of histidine-tagged proteins (42.3-100 kDa). Imidazole in the cell lysis buffer solubilizes protein markers during a 30 s cell lysis step, with an observed protein marker release half-life of 4.46 s. Across hundreds of individual microwells and different microdevices, robust log-linear regression fits (R2 > 0.97) of protein molecular mass and electrophoretic mobility are observed. The protein marker and microparticle system is applied to determine the molecular masses of five endogenous proteins in breast cancer cells (GAPDH, ß-TUB, CK8, STAT3, ER-α), with <20% mass error. Microparticle-delivered protein standards underpin robust, reproducible electrophoretic cytometry that complements single-cell genomics and transcriptomics.

Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products.

Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells play pivotal roles in cell-based therapies. Over the past decades, various methods for expansion and differentiation of stem cells have been developed to satisfy the burgeoning clinical demands. One of the most widely endorsed technologies for producing large cell quantities is using microcarriers (MCs) in bioreactor culture systems. In this review, we focus on microcarriers properties that can manipulate the expansion and fate of stem cells. Here, we provide an overview of commercially available MCs and focus on novel stimulus responsive MCs controlled by temperature, pH and field changes. Different features of MCs including composition, surface coating, morphology, geometry/size, surface functionalization, charge and mechanical properties, and their cellular effects are also highlighted. We then conclude with current challenges and outlook on this promising technology.

Methylmercury levels in commonly consumed fish and methylmercury exposure of children and women of childbearing age in Hong Kong, a high fish consumption community.

BACKGROUND: Despite high fish consumption levels of Hong Kong residents, little is known about the MeHg exposure levels of Hong Kong high-risk populations (i.e. young children and women of childbearing age). OBJECTIVES: To investigate the MeHg levels in fish commonly consumed in Hong Kong and assess the exposure levels of local kindergarten children and women of childbearing age. METHODS: A community-based survey was conducted in randomly recruited local kindergartens. The MeHg concentrations of the most commonly consumed fish items were measured. Based on their fish consumption data, subjects' MeHg exposure levels were estimated and compared with the reference dose (RfD) set by U.S. Environmental Protection Agency. RESULTS: A total of 2917 mother-child pairs were recruited. The MeHg levels of the fish samples ranged from < 2-1498.7 ng/g. Six frozen cod fish samples contained MeHg levels exceeding the local legal limit of 500 ng/g. The median estimated MeHg intake for children and mothers were 0.29 and 0.22 µg/kg bw/wk, respectively. Approximately 16% children and 9% mothers exceeded the RfD. CONCLUSIONS: Apart from frozen cod fish, most fish species commonly consumed in Hong Kong had low MeHg content. Although the majority of our subjects were exposed to low MeHg levels, high fish consumers could still exceed the RfD and are potentially at risk of MeHg toxicity. To avoid excessive MeHg exposure, we suggest that young children and their mothers may consume a variety of locally available fish, but avoid consumption of frozen cod fish.

Rapid Capture and Release of Nucleic Acids through a Reversible Photo-Cycloaddition Reaction in a Psoralen-Functionalized Hydrogel.

Reversible immobilization of DNA and RNA is of great interest to researchers who seek to manipulate DNA or RNA in applications such as microarrays, DNA hydrogels, and gene therapeutics. However, there is no existing system that can rapidly capture and release intact nucleic acids. To meet this unmet need, we developed a functional hydrogel for rapid DNA/RNA capture and release based on the reversible photo-cycloaddition of psoralen and pyrimidines. The functional hydrogel can be easily fabricated through copolymerization of acrylamide with the synthesized allylated psoralen. The psoralen-functionalized hydrogel exhibits effective capture and release of nucleic acids spanning a wide range of lengths in a rapid fashion; over 90 % of the capture process is completed within 1 min, and circa 100 % of the release process is completed within 2 min. We observe no deleterious effects on the hybridization to the captured targets.

Incorporation of Nanoalumina Improves Mechanical Properties and Osteogenesis of Hydroxyapatite Bioceramics.

A handful of work focused on improving the intrinsic low mechanical properties of hydroxyapatite (HA) by various reinforcing agents. However, the big challenge regarding improving mechanical properties is maintaining bioactivity. To address this issue, we report fabrication of apatite-based composites by incorporation of alumina nanoparticles (n-Al2O3). Although numerous studies have used micron or submicron alumina for reinforcing hydroxyapatite, only few reports are available about the use of n-Al2O3. In this study, spark plasma sintering (SPS) method was utilized to develop HA-nAl2O3 dense bodies. Compared to the conventional sintering, decomposition of HA and formation of calcium aluminates phases are restricted using SPS. Moreover, n-Al2O3 acts as a bioactive agent while its conventional form is an inert bioceramics. The addition of n-Al2O3 resulted in 40% improvement in hardness along with a 110% increase in fracture toughness, while attaining nearly full dense bodies. The in vitro characterization of nanocomposite demonstrated improved bone-specific cell function markers as evidenced by cell attachment and proliferation, alkaline phosphatase activity, calcium and collagen detection and nitric oxide production. Specifically, gene expression analysis demonstrated that introduction of n-Al2O3 in HA matrix resulted in accelerated osteogenic differentiation of osteoblast and mesenchymal stem cells, as expression of Runx-2 and OSP showed 2.5 and 19.6 fold increase after 2 weeks (p < 0.05). Moreover, protein adsorption analysis showed enhanced adsorption of plasma proteins to HA-nAl2O3 sample compared to HA. These findings suggest that HA-nAl2O3 could be a prospective candidate for orthopedic applications due to its improved mechanical and osteogenic properties.

Predictability of Supine Radiographs for Determining In-Brace Correction for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To assess whether flexibility as revealed by the supine radiograph, predicts in-brace curve correction. SUMMARY OF BACKGROUND DATA: Currently there is no consensus regarding a standard method to assess curve flexibility and immediate brace effectiveness in treating adolescent idiopathic scoliosis (AIS). Brace fabrication methods may be variable but ideally it should achieve maximal curve correction. Curve flexibility governs the degree of curve correction in-brace and hence dynamic radiographs are commonly performed prior to brace fitting. METHODS: This was a radiographic analysis of AIS patients treated with underarm bracing. Correlation of pre-brace, supine, and immediate in-brace Cobb angles was performed. Relationship with possible contributing factors including age, sex, body height, weight, age at menarche and Risser staging was studied. Major and minor curves were compared independently for correlation but the regression model was constructed based on the major curve only. RESULTS: From 105 patients with mean age of 12.2 ±â€Š1.2 years at brace fitting, supine Cobb angle measurement has significant correlation with immediate in-brace Cobb angle (r = 0.740). Univariate analyses showed no significant relationship with age, weight, height, date of menarche, Risser stage or pre-brace Cobb angle. Our regression model (in-brace Cobb angle = 0.809 × supine Cobb angle) had good fit of the data. CONCLUSION: Supine radiograph predictably determines the flexibility of the scoliotic curve to brace treatment. It can be used as a guideline to determine the amount of correction achievable with brace-wear. The effectiveness of the brace is dependent on the inherent flexibility of the curve rather than its size or type. LEVEL OF EVIDENCE: 3.