Ultrasound in Prenatal Diagnostics and Its Impact on the Epidemiology of Spina Bifida in a National Cohort from Denmark with a Comparison to Sweden

Objectives. The aim of this study was to assess the incidence, the prenatal detection rate by ultrasound, and the pregnancy outcome of spina bifida (SB) in Denmark (DK) in 2008–2015 and to compare results to national data from Sweden. Methods. Data were retrieved from the Danish Fetal Medicine Database, which includes International Classification of Diseases- (ICD-) 10 codes for pre- or postnatally diagnoses and pregnancy outcome. Missing data were obtained from the National Patient Register. Livebirth data with myelomeningocele (MMC) in Sweden were obtained from different databases. Results. There were 234 cases with SB in DK in 2008–2015. The incidence of SB was 4.9 : 10,000; 89% were detected with ultrasound prior to week 22; 90% of these pregnancies were terminated (ToP); 91% were isolated malformations of which 11% showed abnormal karyotype. The incidence of newborns with MMC was 1.3 : 10,000 in Sweden. Conclusions. Ultrasound screening has a major impact on the epidemiology of SB. The prenatal detection rate of SB was high, and most SB cases were isolated and had a normal karyotype. Among women with a prenatal fetal diagnosis of SB, 90% chose to have ToP. The incidence of newborns with SB was higher in Sweden than in DK.

http://ift.tt/2BIYqJF

Retreat from Stress: Rattling in a Planar Coordination

Abstract

Thermoelectric devices convert heat flow to charge flow, providing electricity. Materials for highly efficient devices must satisfy conflicting requirements of high electrical conductivity and low thermal conductivity. Thermal conductivity in caged compounds is known to be suppressed by a large vibration of guest atoms, so-called rattling, which effectively scatters phonons. Here, the crystal structure and phonon dynamics of tetrahedrites (Cu,Zn)₁₂(Sb,As)₄S₁₃ are studied. The results reveal that the Cu atoms in a planar coordination are rattling. In contrast to caged compounds, chemical pressure enlarges the amplitude of the rattling vibration in the tetrahedrites so that the rattling atom is squeezed out of the planar coordination. Furthermore, the rattling vibration shakes neighbors through lone pairs of the metalloids, Sb and As, which is responsible for the low thermal conductivity of tetrahedrites. These findings provide a new strategy for the development of highly efficient thermoelectric materials with planar coordination.

The rattling of Cu atoms in tetrahedrites originates from the chemical pressure inherent in the trigonal-planar environment. When the chemical pressure is increased with reduction of the S₃ triangle area, the rattling amplitude is enlarged. The rattling vibration can shake neighboring metalloid atoms via assistance from the lone pairs of the metalloids.

http://ift.tt/2BJGOxd

Self-Assembly of Enzyme-Like Nanofibrous G-Molecular Hydrogel for Printed Flexible Electrochemical Sensors

Abstract

Conducting hydrogels provide great potential for creating designer shape-morphing architectures for biomedical applications owing to their unique solid–liquid interface and ease of processability. Here, a novel nanofibrous hydrogel with significant enzyme-like activity that can be used as "ink" to print flexible electrochemical devices is developed. The nanofibrous hydrogel is self-assembled from guanosine (G) and KB(OH)₄ with simultaneous incorporation of hemin into the G-quartet scaffold, giving rise to significant enzyme-like activity. The rapid switching between the sol and gel states responsive to shear stress enables free-form fabrication of different patterns. Furthermore, the replication of the G-quartet wires into a conductive matrix by in situ catalytic deposition of polyaniline on nanofibers is demonstrated, which can be directly printed into a flexible electrochemical electrode. By loading glucose oxidase into this novel hydrogel, a flexible glucose biosensor is developed. This study sheds new light on developing artificial enzymes with new functionalities and on fabrication of flexible bioelectronics.

A printed flexible electrochemical sensor is developed based on a novel enzyme-like nanofibrous hydrogel, which is self-assembled from natural product guanosine (G) monomers. The G-molecular hydrogel can serve as templates for hemin-catalyzed formation of polyaniline, and when it coats the gels gives electroconductive soft materials. The unique thixotropic behavior of the gel allows them to be used as inks for 3D printing.

http://ift.tt/2nretaV

Multimodality Imaging of Silica and Silicon Materials In Vivo

Abstract

Recent progress in the development of silica- and silicon-based multimodality imaging nanoprobes has advanced their use in image-guided drug delivery, and the development of novel systems for nanotheranostic and diagnostic applications. As biocompatible and flexibly tunable materials, silica and silicon provide excellent platforms with high clinical potential in nanotheranostic and diagnostic probes with well-defined morphology and surface chemistry, yielding multifunctional properties. In vivo imaging is of great value in the exploration of methods for improving site-specific nanotherapeutic delivery by silica- and silicon-based drug-delivery systems. Multimodality approaches are essential for understanding the biological interactions of nanotherapeutics in the physiological environment in vivo. The aim here is to describe recent advances in the development of in vivo imaging tools based on nanostructured silica and silicon, and their applications in single and multimodality imaging.

Silica and silicon are excellent material platforms for generating multimodality imaging probes for diagnostic and nanotheranostic applications. Being versatile materials with multifunctional properties, they can be extensively used for the creation of novel drug-delivery systems for site-specific nanotherapeutics. When developed into multimodality imaging probes, they are excellent tools for investigating biological interactions of the nanotherapeutics in the physiological environment.

http://ift.tt/2BJGC0X

Discovery of novel 5-methyl-1H-pyrazole derivatives as potential anti-prostate cancer agents: design, synthesis, molecular modeling and biological evaluation

Abstract

Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability comparing with 10e in human liver microsomes.

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Structure optimization via a fragments splicing strategy led to the discovery of a series of 5-methyl-1H-pyrazole derivatives. Part of the compounds showed strong growth inhibition in prostate cancer LNCap cells. AR luciferase reporter gene assay revealed compounds A13 and A14 as potent AR antagonists.

http://ift.tt/2GAbJzP

A comprehensive tool for measuring mammographic density changes over time

Abstract

Background

Mammographic density is a marker of breast cancer risk and diagnostics accuracy. Density change over time is a strong proxy for response to endocrine treatment and potentially a stronger predictor of breast cancer incidence. We developed STRATUS to analyse digital and analogue images and enable automated measurements of density changes over time.

Method

Raw and processed images from the same mammogram were randomly sampled from 41,353 healthy women. Measurements from raw images (using FDA approved software iCAD) were used as templates for STRATUS to measure density on processed images through machine learning. A similar two-step design was used to train density measures in analogue images. Relative risks of breast cancer were estimated in three unique datasets. An alignment protocol was developed using images from 11,409 women to reduce non-biological variability in density change. The protocol was evaluated in 55,073 women having two regular mammography screens. Differences and variances in densities were compared before and after image alignment.

Results

The average relative risk of breast cancer in the three datasets was 1.6 [95% confidence interval (CI) 1.3–1.8] per standard deviation of percent mammographic density. The discrimination was AUC 0.62 (CI 0.60–0.64). The type of image did not significantly influence the risk associations. Alignment decreased the non-biological variability in density change and re-estimated the yearly overall percent density decrease from 1.5 to 0.9%, p < 0.001.

Conclusions

The quality of STRATUS density measures was not influenced by mammogram type. The alignment protocol reduced the non-biological variability between images over time. STRATUS has the potential to become a useful tool for epidemiological studies and clinical follow-up.

http://ift.tt/2DS6I43

Serum Soluble Vascular Cell Adhesion Molecule-1 Overexpression Is a Disease Marker in Patients with First-Time Diagnosed Antinuclear Antibodies: A Prospective, Observational Pilot Study

Objective. Antinuclear antibodies (ANA) serve as screening tests for connective tissue diseases but have low specificity. In this pilot study, we aimed to identify patients with first-time positive ANA and musculoskeletal complaints and correlate serum soluble vascular adhesion molecules as biomarkers. Methods. Prospective, observational study with 100 ANA-positive patients, comparing them to age- and gender-matched healthy controls (HC, ), was conducted. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were measured. A subgroup of patients with systemic sclerosis (SSc) treated with immunosuppressants was followed over 10 months. Results. Patients belonged to three main entities: rheumatoid arthritis (RA, ), collagen diseases (CD, ) also including systemic sclerosis (SSc, ), and other autoimmune diseases (). sICAM-1 was similar among groups. sELAM-1 was elevated by 1.9-fold in only in SSc. sVCAM-1 was elevated by 3.1-fold in RA and by 3.3-fold in CD and in other autoimmune diseases by 3.4-fold. Seven SSc patients with immunosuppression had a 2.7-fold increased sVCAM-1 at baseline and reached the levels of healthy controls after 5 months, while CRP, ESR, and clinical parameters remained unchanged. Conclusion. Our study suggests that sVCAM-1 is a disease marker independent of standard serum parameters in several rheumatic diseases. This study is registered with EU PAS Register number: EUPAS22154.

http://ift.tt/2nrbIX7