Characteristics of intussusception among children in Korea: a nationwide epidemiological study.

BACKGROUND: Intussusception is a gastrointestinal condition in which early treatment is critical. Although its epidemiology and comorbidities have been studied, few studies have included the entire pediatric population of a country. Therefore, we aimed to analyze the epidemiologic features of pediatric intussusception patients and identify comorbidities associated with intussusception in South Korea, using the public health database. METHODS: We analyzed the data of children below 18 years of age, from the national database of South Korea, who were diagnosed with intussusception and managed such as air reduction or surgical methods from 2008 to 2016. Patients were categorized into six groups based on the comorbid diseases. Patients with structural lesion in gastrointestinal tract were divided diagnosis or diagnosis code. RESULTS: The number of patients diagnosed with intussusception were 25,023 (16,024 males, 64.0%). Of them, the highest percentage was patients aged between 2 and 36 months (20,703; 82.7%). The incidence per 100,000 individuals aged up to 2 years was 196.7. The number of males were 16,024 (64.0%) and were almost twice the number of 8999 (36.0%) female patients. The maximum number of cases (n = 2517; 10.1%) were seen in September, followed by July (n = 2469; 9.9%). In February, the number of cases was lowest at 1448 (5.8%) patients (P < 0.001). The number of patients with structural lesions of the gastrointestinal tract that could lead to intussusception was 1207 (4.8%), while patients with acute gastrointestinal infectious disease were 4541 (18.1%). Among the structural lesions of the gastrointestinal tract that could be the leading cause of intussusception, lymphadenopathy was the most common, seen in 462 (56.6%) patients and an appendix-related condition was seen in 260 (31.9%) patients. Infectious diseases were more common in the younger children, while systemic diseases were more common in the older. CONCLUSION: We confirmed that pediatric intussusception in South Korea shows a seasonal tendency, which is age-dependent and is associated with an exposure to infectious agents. Some infectious pathogens and underlying diseases might play an important role in the pathophysiology of intussusception.

Fabrication and Characterization of Finite-Size DNA 2D Ring and 3D Buckyball Structures.

In order to incorporate functionalization into synthesized DNA nanostructures, enhance their production yield, and utilize them in various applications, it is necessary to study their physical stabilities and dynamic characteristics. Although simulation-based analysis used for DNA nanostructures provides important clues to explain their self-assembly mechanism, structural function, and intrinsic dynamic characteristics, few studies have focused on the simulation of DNA supramolecular structures due to the structural complexity and high computational cost. Here, we demonstrated the feasibility of using normal mode analysis for relatively complex DNA structures with larger molecular weights, i.e., finite-size DNA 2D rings and 3D buckyball structures. The normal mode analysis was carried out using the mass-weighted chemical elastic network model (MWCENM) and the symmetry-constrained elastic network model (SCENM), both of which are precise and efficient modeling methodologies. MWCENM considers both the weight of the nucleotides and the chemical bonds between atoms, and SCENM can obtain mode shapes of a whole structure by using only a repeated unit and its connectivity with neighboring units. Our results show the intrinsic vibrational features of DNA ring structures, which experience inner/outer circle and bridge motions, as well as DNA buckyball structures having overall breathing and local breathing motions. These could be used as the fundamental basis for designing and constructing more complicated DNA nanostructures.

Ternary and senary representations using DNA double-crossover tiles.

The information capacity of DNA double-crossover (DX) tiles was successfully increased beyond a binary representation to higher base representations. By controlling the length and the position of DNA hairpins on the DX tile, ternary and senary (base-3 and base-6) digit representations were realized and verified by atomic force microscopy. Also, normal mode analysis was carried out to study the mechanical characteristics of each structure.

Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges.

Delivering therapeutics to the central nervous system (CNS) is difficult because of the blood-brain barrier (BBB). Therapeutic delivery across the tight junctions of the BBB can be achieved through various endogenous transportation mechanisms. Receptor-mediated transcytosis (RMT) is one of the most widely investigated and used methods. Drugs can hijack RMT by expressing specific ligands that bind to receptors mediating transcytosis, such as the transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (INSR). Cell-penetrating peptides and viral components originating from neurotropic viruses can also be utilized for the efficient BBB crossing of therapeutics. Exosomes, or small extracellular vesicles, have gained attention as natural nanoparticles for treating CNS diseases, owing to their potential for natural BBB crossing and broad surface engineering capability. RMT-mediated transport of exosomes expressing ligands such as LDLR-targeting apolipoprotein B has shown promising results. Although surface-modified exosomes possessing brain targetability have shown enhanced CNS delivery in preclinical studies, the successful development of clinically approved exosome therapeutics for CNS diseases requires the establishment of quantitative and qualitative methods for monitoring exosomal delivery to the brain parenchyma in vivo as well as elucidation of the mechanisms underlying the BBB crossing of surface-modified exosomes.

Fibres and films made from DNA and CTMA-modified DNA embedded with gold nanorods and organic light-emitting materials.

The scaffolding of deoxyribonucleic acid (DNA) makes DNA molecules effective templates for hosting various types of nanomaterials. Recently, electrospun fibres formed by a variety of polymers have begun to see use in a number of applications, such as filtration in energy applications, insulation in thermodynamics and protein scaffolding in biomedicine. In this study, we constructed electrospun fibres and thin films made of DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA (CDNA) embedded with dyes, organic light-emitting materials (OLEMs), and gold nanorods (GNRs). These materials provide significant advantages, including selectivity of dimensionality, solubility in organic and inorganic solvents, and functionality enhancement. In addition, coaxial fibres made of CDNA were constructed to demonstrate the feasibility of constructing relatively complex fibres with an electrospinner. To determine the basic physical characteristics of the fibres and thin films containing GNRs and OLEMs, we conducted current measurements, photoluminescence (PL) measurements, X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible (UV-Vis) spectroscopy. The currents in DNA and CDNA were found to exhibit Ohmic behaviour, while the PL emission could be controlled by OLEMs. In addition, the XPS provided the chemical configuration of samples, and the UV-Vis spectra revealed the plasmon resonance of GNR. Due to their simple fabrication and enhanced functionality, these DNA and CDNA fibres and thin films could be used in various devices (e.g., filters or blocking layers) and sensors (e.g., gas detectors and bio sensors) in a number of industries.

Multi-Domains in a Single Lattice Formed by DNA Self-Assembly.

Using sequence programmability and the characteristics of self-assembly, DNA has been utilized in the construction of various nanostructures and the placement of specific patterns on lattices. Even though many complex structures and patterns formed by DNA assembly have been reported, the fabrication of multi-domain patterns in a single lattice has rarely been discussed. Multi-domains possessing specifically designed patterns in a single lattice provide the possibility to generate multiple patterns that enhance the pattern density in a given single lattice. Here, we introduce boundaries to construct double- and quadruple-domains with specific patterns in a single lattice and verify them with atomic force microscopy. ON, OFF, and ST (stripe) patterns on a lattice are made of DNA tiles with hairpins (ON), without hairpins (OFF), and alternating DNA tiles without and with hairpins (formed as a stripe, ST). For double- and quadruple-domain lattices, linear and cross boundaries were designed to fabricate two (e.g., ON and OFF, ON and ST, and OFF and ST) and four (OFF, ST, OFF, and ON) different types of patterns in single lattices, respectively. In double-domain lattices, each linear boundary is placed between two different domains. Similarly, four linear boundaries connected with a seed tile (i.e., a cross boundary) can separate four domains in a single lattice in quadruple-domain lattices. Due to the presence of boundaries, the pattern growth directions are different in each domain. The experimentally obtained multi-domain patterns agree well with our design. Lastly, we propose the possibility of the construction of a hexadomain lattice through the mapping from hexagonal to square grids converted by using an axial coordinate system. By proposing a hexadomain lattice design, we anticipate the possibility to extend to higher numbers of multi-domains in a single lattice, thereby further increasing the information density in a given lattice.

Nanomaterial-Embedded DNA Films on 2D Frames.

Recently, 3D printing has provided opportunities for designing complex structures with ease. These printed structures can serve as molds for complex materials such as DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA that have easily tunable functionalities via the embedding of various nanomaterials such as ions, nanoparticles, fluorophores, and proteins. Herein, we develop a simple and efficient method for constructing DNA flat and curved films containing water-soluble/thermochromatic dyes and di/trivalent ions and CTMA-modified DNA films embedded with organic light-emitting molecules (OLEM) with the aid of 2D/3D frames made by a 3D printer. We study the Raman spectra, current, and resistance of Cu2+-doped and Tb3+-doped DNA films and the photoluminescence of OLEM-embedded CTMA-modified DNA films to better understand the optoelectric characteristics of the samples. Compared to pristine DNA, ion-doped DNA films show noticeable variation of Raman peak intensities, which might be due to the interaction between the ion and phosphate backbone of DNA and the intercalation of ions in DNA base pairs. As expected, ion-doped DNA films show an increase of current with an increase in bias voltage. Because of the presence of metallic ions, DNA films with embedded ions showed relatively larger current than pristine DNA. The photoluminescent emission peaks of CTMA-modified DNA films with OLEMRed, OLEMGreen, and OLEMBlue were obtained at the wavelengths of 610, 515, and 469 nm, respectively. Finally, CIE color coordinates produced from CTMA-modified DNA films with different OLEM color types were plotted in color space. It may be feasible to produce multilayered DNA films as well. If so, multilayered DNA films embedded with different color dyes, ions, fluorescent materials, nanoparticles, proteins, and drug molecules could be used to realize multifunctional physical devices such as energy harvesting and chemo-bio sensors in the near future.

Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.

Large-scale conformational changes are essential for proteins to function properly. Given that these transition events rarely occur, however, it is challenging to comprehend their underlying mechanisms through experimental and theoretical approaches. In this study, we propose a new computational methodology called internal coordinate normal mode-guided elastic network interpolation (ICONGENI) to predict conformational transition pathways in proteins. Its basic approach is to sample intermediate conformations by interpolating the interatomic distance between two end-point conformations with the degrees of freedom constrained by the low-frequency dynamics afforded by normal mode analysis in internal coordinates. For validation of ICONGENI, it is applied to proteins that undergo open-closed transitions, and the simulation results (i.e., simulated transition pathways) are compared with those of another technique, to demonstrate that ICONGENI can explore highly reliable pathways in terms of thermal and chemical stability. Furthermore, we generate an ensemble of transition pathways through ICONGENI and investigate the possibility of using this method to reveal the transition mechanisms even when there are unknown metastable states on rough energy landscapes.

Demonstration of elementary functions via DNA algorithmic self-assembly.

Target-oriented cellular automata with computation are the primary challenge in the field of DNA algorithmic self-assembly in connection with specific rules. We investigate the feasibility of using the principle of cellular automata for mathematical subjects by using specific logic gates that can be implemented into DNA building blocks. Here, we connect the following five representative elementary functions: (i) enumeration of multiples of 2, 3, and 4 (demonstrated via R094, R062, and R190 in 3-input/1-output logic rules); (ii) the remainder of 0 and 1 (R132); (iii) powers of 2 (R129); (iv) ceiling function for n/2 and n/4 (R152 and R144); and (v) analogous pattern of annihilation (R184) to DNA algorithmic patterns formed by specific rules. After designing the abstract building blocks and simulating the generation of algorithmic lattices, we conducted an experiment as follows: designing of DNA tiles with specific sticky ends, construction of DNA lattices via a two-step annealing method, and verification of expected algorithmic patterns on a given DNA lattice using an atomic force microscope (AFM). We observed representative patterns, such as horizontal and diagonal stripes and embedded triangles, on the given algorithmic lattices. The average error rates of individual rules are in the range of 8.8% (R184) to 11.9% (R062), and the average error rate for all the rules was 10.6%. Interpretation of elementary functions demonstrated through DNA algorithmic patterns could be extended to more complicated functions, which may lead to new insights for achieving the final answers of functions with experimentally obtained patterns.

Effect of a new Lactobacillus plantarum product, LRCC5310, on clinical symptoms and virus reduction in children with rotaviral enteritis.

BACKGROUND: Rotavirus is one of the most common causes of infantile enteritis. In common enterocolitis, probiotic organisms, including Lactobacilli, are effective in treating diarrhea. A new species, Lactobacillus plantarum (LRCC5310), which was shown to inhibit the adherence and proliferation of rotavirus in the small intestine through animal experiments, was investigated for the efficacy and safety of patients with rotaviral enteritis. METHODS: LRCC5310 (Group I) and control (Group II) groups consisting of children who were hospitalized for rotaviral enteritis were compared, and the medical records of patients (Group III) who were hospitalized for rotaviral enteritis during the same study period were retrospectively analyzed. Clinical symptoms were compared and stool samples were collected to compare changes in virus multiplication between Groups I and II. RESULTS: Groups I, II, and III comprised 15, 8, and 27 children, respectively. There were no differences in clinical information among the groups at admission. In Group I, a statistically significant improvement was noted in the number of patients with diarrhea, number of defecation events on Day 3, and total diarrhea period as opposed to Group II (P = .033, P = .003, and P = .012, respectively). The improvement of Vesikari score in Group I was greater than that in the other groups (P = .076, P = .061, and P = .036, respectively). Among rotavirus genotypes, 9 (22.5%) strains and 8 (20.0%) strains belonged to the G9P8 and G1P8 genotypes, respectively. The virus reduction effect, as confirmed via stool specimens, was also greater in Group I. No significant side effects were noted in infants. CONCLUSION: LRCC5310 improved clinical symptoms, including diarrhea and Vesikari score, and inhibited viral proliferation in rotaviral gastroenteritis.

Normal mode analysis of Zika virus.

In recent years, Zika virus (ZIKV) caused a new pandemic due to its rapid spread and close relationship with microcephaly. As a result, ZIKV has become an obvious global health concern. Information about the fundamental viral features or the biological process of infection remains limited, despite considerable efforts. Meanwhile, the icosahedral shell structure of the mature ZIKV was recently revealed by cryo-electron microscopy. This structural information enabled us to simulate ZIKV. In this study, we analyzed the dynamic properties of ZIKV through simulation from the mechanical viewpoint. We performed normal mode analysis (NMA) for a dimeric structure of ZIKV consisting of the envelope proteins and the membrane proteins as a unit structure. By analyzing low-frequency normal modes, we captured intrinsic vibrational motions and defined basic vibrational properties of the unit structure. Moreover, we also simulated the entire shell structure of ZIKV at the reduced computational cost, similar to the case of the unit structure, by utilizing its icosahedral symmetry. From the NMA results, we can not only comprehend the putative dynamic fluctuations of ZIKV but also verify previous inference such that highly mobile glycosylation sites would play an important role in ZIKV. Consequently, this theoretical study is expected to give us an insight on the underlying biological functions and infection mechanism of ZIKV.

Normal mode-guided transition pathway generation in proteins.

The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI) that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this.

Dynamic characteristics of a flagellar motor protein analyzed using an elastic network model.

At the base of a flagellar motor, its rotational direction and speed are regulated by the interaction between rotor and stator proteins. A switching event occurs when the cytoplasmic rotor protein, called C-ring, changes its conformation in response to binding of the CheY signal protein. The C-ring structure consists of FliG, FliM, and FliN proteins and its conformational changes in FliM and FliG including HelixMC play an important role in switching the motor direction. Therefore, clarifying their dynamic properties as well as conformational changes is a key to understanding the switching mechanism of the motor protein. In this study, to elucidate dynamic characteristics of the C-ring structure, both harmonic (intrinsic vibration) and anharmonic (transition pathway) analyses are conducted by using the symmetry-constrained elastic network model. As a result, the first three normal modes successfully capture the essence of transition pathway from wild type to CW-biased state. Their cumulative square overlap value reaches up to 0.842. Remarkably, it is also noted from the transition pathway that the cascade of interactions from the signal protein to FliM to FliG, highlighted by the major mode shapes from the first three normal modes, induces the reorientation (∼100° rotation of FliGC5) of FliG C-terminal that directly interacts with the stator protein. Presumably, the rotational direction of the motor protein is switched by this substantial change in the stator-rotor interaction.