Polycyclic aromatic hydrocarbons and changes in brain cortical thickness and an Alzheimer's disease-specific marker for cortical atrophy in adults: A longitudinal neuroimaging study of the EPINEF cohort.

Although several epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) may induce brain atrophy, no longitudinal study has investigated the effect of PAH exposure on brain structural changes. This study examined the longitudinal associations between urinary PAH metabolites and brain cortical thickness. We obtained urinary concentrations of PAH metabolites and brain magnetic resonance images from 327 adults (≥50 years of age) without dementia at baseline and 3-year follow-up. We obtained whole-brain and regional cortical thicknesses, as well as an Alzheimer's disease (AD)-specific marker for cortical atrophy (a higher score indicated a greater similarity to patients with AD) at baseline and follow-up. We built a linear mixed-effect model including each of urinary PAH metabolites as the time-varying exposure variable of interest. We found that increases in urinary concentrations of 1-hydroxypyrene (ß = -0.004; 95% CI, -0.008 to -0.001) and 2-hydroxyfluorene (ß = -0.011; 95% CI, -0.015 to -0.006) were significantly associated with a reduced whole-brain cortical thickness. A urinary concentration of 2-hydroxyfluorene was significantly associated with an increased AD-specific cortical atrophy score (ß = 2.031; 95% CI, 0.512 to 3.550). The specific brain regions showing the association of urinary concentrations of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, or 2-hydroxyfluorene with cortical thinning were the frontal, parietal, temporal, and cingulate lobes. These findings suggested that exposure to PAHs may reduce brain cortical thickness and increase the similarity to AD-specific cortical atrophy patterns in adults.

Development of breast phantoms using a 3D printer and glandular dose evaluation.

In this study, breast phantoms were fabricated by emulating glandular and adipose tissues separately using a three-dimensional (3D) printer. In addition, direct and quantitative glandular dose evaluations were performed. A quantitative method was developed to evaluate the glandular and adipose tissues separately when performing glandular dose evaluations. The variables used for glandular dose evaluation were breast thickness, glandular tissue ratio, and additional filter materials. The values obtained using a Monte Carlo simulation and those measured using a glass dosimeter were compared and analyzed. The analysis showed that as the glandular tissue ratio increased, the dose decreased by approximately 10%, which is not a significant variation. The comparison revealed that the simulated values of the glandular dose were approximately 15% higher than the measured values. The use of silver and rhodium filters resulted in a mean simulated dose of 1.00 mGy and 0.72 mGy, respectively, while the corresponding mean measured values were 0.89 mGy ± 0.03 mGy and 0.62 mGy ± 0.02 mGy. The mean glandular dose can be reliably evaluated by comparing the simulated and measured values.

The effect of body fatness on regional brain imaging markers and cognitive function in healthy elderly mediated by impaired glucose metabolism.

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (ß = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (ß = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (ß = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (ß = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (ß = -0.005; BC 95% CI = -0.013 to -0.001/ß = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (ß = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (ß = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (ß = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.

Prediction of Gestational Diabetes Mellitus in Pregnant Korean Women Based on Abdominal Subcutaneous Fat Thickness as Measured by Ultrasonography.

BACKGROUND: This study was performed to verify the correlation between abdominal subcutaneous fat thickness (ASFT) measured by ultrasonography (US) during the first trimester of pregnancy and gestational diabetes mellitus (GDM) of the second trimester in Korean women and to establish a standard of ASFT for predicting GDM. METHODS: A total of 333 singleton pregnant women participated in this study. Their ASFT was measured by US during the 10⁺6 to 13⁺6 weeks of pregnancy; then a GDM confirmatory test (100 g oral glucose tolerance test) was conducted during the 24 to 28 week period of pregnancy. Based on the GDM tests, comparative analyses of the ages of the subjects, pre-pregnancy body mass index (BMI), and weight gain during pregnancy were conducted. RESULTS: The ages of the subjects and weight gains during pregnancy were not correlated to the GDM of the second trimester of pregnancy, but the pre-pregnancy BMIs (22±3.3 kg/m²) and the ASFT (1.9±0.5 cm) measurements between the control group and subjects during the first trimester of pregnancy were found to show significant differences (P<0.001). The cut-off value of the ASFT for predicting GDM was determined to be 2.4 cm (area under the curve=0.90, sensitivity 75.61%, specificity 91.78%, P<0.001). The odds ratio was 2.91 (95% confidence interval, 1.07 to 7.92; P=0.034), which was higher than the 2.4 cm ASFT. CONCLUSION: It was determined that ASFT as measured by US during the first trimester of pregnancy can be used to predict the risk of developing GDM during the second trimester of pregnancy and for prognosis.

Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications.

Here we communicate the generation of biomimetically grown apatite spheres from aggregated bioglass nanoparticles and the potential properties applicable for drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of bioglass (85%SiO2-15%CaO) in a mineralizing medium show an intriguing dynamic phenomenon - aggregation, mineralization to apatite, integration and growth into micron-sized (1.5-3µm) spheres. During the progressive ionic dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal composition, and the physico-chemical properties (porosity, surface area, and charge) change dynamically. With increasing reaction period, the apatite becomes more crystallized with increased crystallinity and crystal size, and gets a composition closer to the stoichiometry. The developed microspheres exhibit hierarchical surface nanostructure, negative charge (ς-potential of -20mV), and ultrahigh mesoporosity (mesopore size of 6.1nm, and the resultant surface area of 63.7m2/g and pore volume of 0.153cm3/g) at 14days of mineralization, which are even higher than those of its precursor bioglass nanoparticles. Thanks to these properties, the biomimetic mineral microspheres take up biological molecules effectively, i.e., loading capacity of positive-charged protein is over 10%. Of note, the release is highly sustainable at a constant rate, i.e., profiling almost 'zero-order' kinetics for 4weeks, suggesting the potential usefulness as protein delivery systems. The biomimetic mineral microspheres hold some remnant Si in the core region, and release calcium, phosphate, and silicate ions over the test period, implying the long-term ionic-related therapeutic functions. The mesenchymal stem cells favour the biomimetic spheres with an excellent viability. Due to the merit of sizes (a few micrometers), the spheres can be intercalated into cells, mediating cellular interactions in 3D cell-spheroid engineering, and also can stimulate osteogenic differentiation of cells when incorporated into cell-laden gels. The intriguing properties observed in this study, including biomimetic composition, high mesoporosity, release of therapeutic ions, effective loading and long-term release of proteins, and diverse yet favorable 3D cellular interactions, suggest great potential of the newly developed biomimetic microspheres in biomedical applications, such as drug delivery and cell/tissue engineering. STATEMENT OF SIGNIFICANCE: This work reports the generation of apatite spheres with a few micrometers in size biomimetically grown from bioactive glass nanoparticles, through a series of intriguing yet unprecedented phenomenon involving aggregation of nanoparticles, mineralization and sphere growth. The mineral microspheres possess some unique physico-chemical properties including mesoporosity, ultrahigh surface area, and therapeutic ionic release. Furthermore, the spheres show excellent loading and delivery capacity of protein molecules, and mediate favorable cellular interactions in 2D and 3D culture conditions, demonstrating a future multifunctional microcarrier platform for the therapeutics delivery and cell/tissue engineering.

Normal intracranial BS/BSOB ratio values in the first trimester of single gestations with live fetuses in a Korean population.

AIM: The purpose of this study was to determine the normal length of the brainstem (BS) in Korean fetuses and to evaluatethe usefulness of the routine measurement of BS size in the first trimester of pregnancy for the early detection of spina bifida. MATERIAL AND METHODS: A total of 2,621 normal singleton pregnant Korean women at 10+6 to 13+6 weeks of gestation were selected for this retrospective cross-sectional study. Ultrasonography was used to measure the length of the longest vertical depth diameter of the BS and brainstem-occipital bone (BSOB) in order to obtain the BS to BSOB ratio. RESULTS: The best indicators for spina bifida ranged from 1.00±0.24 mm to 4.70±0.46 mm for the BS and from 2.90±0.36 mm to 8.50±0.92 mm for the BSOB. For the gestational period, BS (R=0.70) and BSOB (R=0.81) values were considered statistically significant (p<.0001). The value of the BS to BSOB ratio was <1.0 in normal fetuses, and was not correlated with the gestational age. CONCLUSION: Measurement of BS and BSOB diameter in the first trimester is thought to provide the best reference marker for evaluating the posterior brain for diagnosis of spina bifida.

Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering.

Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

Carbon nanotube-collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors.

Microenvironments provided by three-dimensional (3-D) hydrogels mimic native tissue conditions, supplying appropriate physical cues for regulating stem cell behaviors. Here, we focused on carbon nanotubes (CNTs) dispersed within collagen hydrogels to provide 3-D microenvironmental conditions for mesenchymal stem cells (MSCs) in stimulating biological functions for neural regeneration. Small concentrations of CNTs (0.1-1wt.%) did not induce toxicity to MSCs, and even improved the proliferative potential of the cells. MSCs cultured within the CNT-collagen hydrogel expressed considerable levels of neural markers, including GAP43 and ßIII tubulin proteins by immunostaining as well as GAP43 and synapse I genes by reverse transcriptase polymerase chain reaction (RT-PCR). Of note was that neurotrophic factors, particularly nerve growth factor and brain derived neurotrophic factor, were significantly promoted by the incorporation of CNTs as confirmed by RT-PCR and Western blot analysis. A model experiment involving neuritogenesis of PC12 cells influenced by those releasing neurotrophic factors from MSCs cultured within the CNT-collagen hydrogel demonstrated the significant enhancement in neurite outgrowth behaviors. Taken together, collagen hydrogel provides excellent 3-D conditions for MSC growth, and a small incorporation of CNTs within the hydrogel significantly stimulates MSC expression of neural markers and secretion of neurotrophic factors.

A novel in vivo platform for studying alveolar bone regeneration in rat.

Alveolar bone regeneration is a significant challenge in dental implantation. Novel biomaterials and tissue-engineered constructs are under extensive development and awaiting in vivo animal tests to find clinical endpoint. Here, we establish a novel in vivo model, modifying gingivoperiosteoplasty in rat for the alveolar bone regeneration. Rat premaxillary bone defects were filled with silk scaffold or remained empty during the implantation period (up to 6 weeks), and harvested samples were analyzed by micro-computed tomography and histopathology. Empty defects showed increased but limited new bone formation with increasing implantation period. In defects implanted with silk sponge, the bone formation was significantly greater than that of empty defect, indicating an effective role of silk scaffold in the defect model. The modified premaxillary defect model in rat is simple to perform, while mimicking the clinical conditions, finding usefulness for the development of biomaterials and tissue-engineered constructs targeting alveolar bone regeneration in dental implantation.