Characteristics of Cognitive Function Changes and Related Factors in Individuals With Cognitive Impairment During the Pandemic of COVID-19: A Retrospective Chart Review Study.

OBJECTIVE: This study aimed to explore the characteristics and factors related to changes in cognitive function in vulnerable individuals with cognitive impairment during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Among patients who visited a local university hospital with subjective cognitive complaints, those who had been tested for cognitive function at least once after the onset of COVID-19 and tested regularly at least three times within the last 5 years were included (1st, the initial screening; 2nd, the test immediately before the COVID-19 pandemic; 3rd, the most recent test after the pandemic). Finally, 108 patients were included in this study. They were divided into groups according to whether the Clinical Dementia Rating (CDR) was maintained/improved and deteriorated. We investigated the characteristics of the changes in cognitive function and related factors during COVID-19. RESULTS: When comparing CDR changes before and after COVID-19, there was no significant difference between the two groups (p=0.317). Alternatively, the main effect of the time when the test was conducted was significant (p<0.001). There was also a significant difference in the interaction between the groups and time. When the effect of the interaction was analyzed, the CDR score of the maintained/ improved group significantly decreased before COVID-19 (1st-2nd) (p=0.045). After COVID-19 (2nd-3rd), the CDR score of the deteriorated group was significantly higher than that of the maintained/improved group (p<0.001). Mini-Mental State Examination recall memory and changes in activity during COVID-19 were significantly associated with CDR deterioration. CONCLUSION: Memory dysfunction and decreased activity during the COVID-19 pandemic are strongly related to the deterioration of cognitive impairment.

Quantitation of propionic acid in emmental cheese products by direct solvent extraction.

Propionic acid (PA) is commonly present in Emmental cheese (EM) with relatively high concentration. Even though PA is allowed as GRAS in the USA, it may cause neurological disorders if it is consumed excessively. The maximum level of the preservative PA in cheese is set at 3.0 g/kg by the Korean Food Code. Also, the minimum level of PA in EM (150 mg / 100 g) was set by Codex in 1967. Therefore, PA monitoring in EM, with relatively high level of intrinsic PA, is necessary to recommend the sound use of the PA in the EM ripened. The current official PA analysis method consisting of steam distillation and solvent extraction / evaporation, is too cumbersome to be handled in sample preparation process. In this study, acidic acetone-based direct extraction method was successfully applied to 12 EM samples for the determination of PA level.

A Study on Verification of Equivalence and Effectiveness of Non-Pharmacologic Dementia Prevention and Early Detection Contents : Non-Randomly Equivalent Design.

OBJECTIVE: The aim of this study was to verify the equivalence and effectiveness of the tablet-administered Korean Repeatable Battery for the Assessment of Neuropsychological Status (K-RBANS) for the prevention and early detection of dementia. METHODS: Data from 88 psychiatry and neurology patient samples were examined to evaluate the equivalence between tablet and paper administrations of the K-RBANS using a non-randomly equivalent group design. We calculated the prediction scores of the tablet-administered K-RBANS based on demographics and covariate-test scores for focal tests using norm samples and tested format effects. In addition, we compared the receiver operating characteristic curves to confirm the effectiveness of the K-RBANS for preventing and detecting dementia. RESULTS: In the analysis of raw scores, line orientation showed a significant difference (t=-2.94, p<0.001), and subtests showed small to large effect sizes (0.04-0.86) between paper- and tablet-administered K-RBANS. To investigate the format effect, we compared the predicted scaled scores of the tablet sample to the scaled scores of the norm sample. Consequently, a small effect size (d≤0.20) was observed in most of the subtests, except word list and story recall, which showed a medium effect size (d=0.21), while picture naming and subtests of delayed memory showed significant differences in the one-sample t-test. In addition, the area under the curve of the total scale index (TSI) (0.827; 95% confidence interval, 0.738-0.916) was higher than that of the five indices, ranging from 0.688 to 0.820. The sensitivity and specificity of TSI were 80% and 76%, respectively. CONCLUSION: The overall results of this study suggest that the tablet-administered K-RBANS showed significant equivalence to the norm sample, although some subtests showed format effects, and it may be used as a valid tool for the brief screening of patients with neuropsychological disorders in Korea.

Dysfunctional activity of classical DNA end-joining renders acquired resistance to carboplatin in human ovarian cancer cells.

Ovarian cancer is the deadliest gynecological malignancy worldwide. Although chemotherapy is required as the most standard treatment strategy for ovarian cancer, the survival rates are very low, largely because of high incidence of recurrence due to resistance to conventional surgery and genotoxic chemotherapies. Carboplatin-resistant ovarian cancer cells were generated by continuous treatment over six months. Carboplatin-resistance induced morphological alterations and promoted the rates of proliferation and migration of SKOV3 compared to the parental cells. Interestingly, carboplatin-resistant SKOV3 showed the high levels of γH2AX foci formed at the basal level, and the levels of γH2AX foci remained even after the recovery time, suggesting that the DNA damage response and repair machinery were severely attenuated by carboplatin-resistance. Surprisingly, the expression levels of XRCC4, a critical factor in non-homologous end joining (NHEJ) DNA repair, were significantly decreased in carboplatin-resistant SKOV3 compared with those in non-resistant controls. Furthermore, restoration of NHEJ in carboplatin-resistant SKOV3 by suppression of ABCB1 and/or AR re-sensitized carboplatin-resistant cells to genotoxic stress and reduced their proliferation ability. Our findings suggest that attenuation of the NHEJ DNA repair machinery mediated by resistance to genotoxic stress might be a critical cause of chemoresistance in patients with ovarian cancer.

Testicular atrophy after mumps orchitis: ultrasonographic findings.

PURPOSE: The purpose of this study was to describe the ultrasonographic findings of testicular atrophy after mumps orchitis. METHODS: We retrospectively reviewed the case files of eight patients (14 to 24 years old; mean, 17 years) with mumps orchitis and testicular atrophy who were treated between January 2011 and September 2017. On gray-scale and color Doppler, the ultrasonographic features of volume, shape, echogenicity, and degree of blood flow in the testes were analyzed as part of both initial and follow-up ultrasonography. The duration between the initial diagnosis of mumps orchitis and the ultrasonographic diagnosis of testicular atrophy after mumps orchitis ranged from 25 to 230 days (mean, 95.9 days). RESULTS: Of the eight patients with testicular atrophy after mumps orchitis, the testes were affected unilaterally in seven patients (6 right-sided and 1 left-sided) and bilaterally in one patient. The affected testes (n=9) were 23%-55% (mean, 44.7%) smaller in volume (mean, 6.3±2.0 mL) than the contralateral normal testes (n=7) (mean, 10.8±2.3 mL) on follow-up ultrasonography (P=0.001). The shape of the atrophic testes was oblong in seven cases and elliptical in two cases. The atrophic testes were either heterogeneously hypoechoic with multiple hyperechoic islands (n=7) or heterogeneously hyperechoic (n=2). On follow-up color Doppler ultrasonography, the degree of vascularity of the atrophic testis was either similar to (n=3) or lower than (n=6) that of the contralateral testis. CONCLUSION: On ultrasonography, atrophic testes after mumps orchitis tended to exhibit an oblong shape, heterogeneous low echogenicity with multiple hyperechoic islands, and decreased vascularity.

Effect of High-Speed Blade Coating on Electrical Characteristics in Polymer Based Transistors.

We explore the effect of high-speed blade coating on electrical characteristics of conjugated polymer-based thin-film transistors (TFTs). As the blade-coating speed increased, the thickness of the polymer thin-film was naturally increased while the surface roughness was found to be unchanged. Polymer TFTs show two remarkable tendencies on the magnitude of field-effect mobility with increasing blade-coating speed. As the blade-coating speed increased up to 2 mm/s, the fieldeffect mobility increased to 4.72 cm²V-1s-1. However, when the coating speed reached 6 mm/s beyond 2 mm/s, the field-effect mobility rather decreased to 3.18 cm²V-1s-1. The threshold voltage was positively shifted from 2.09 to 8.29 V with respect to increase in blade-coating speed.

Diazirine photocrosslinking recruits activated FTO demethylase complexes for specific N(6)-methyladenosine recognition.

N(6)-methyladenosine (m(6)A) is a prevalent modification of RNAs. m(6)A exists in mRNA and plays an important role in RNA biological pathways and in RNA epigenetic regulation. We applied diazirine photocrosslinking to the event of m(6)A recognition mediated by the fat mass and obesity associated (FTO) demethylase. A highly photoreactive diazirine adjacent to m(6)A on the RNA successfully recruited activated FTO complexes with an m(6)A preference. The process of recognition of m(6)A via FTO using diazirine photocrosslinking was controlled by the α-ketoglutarate (α-KG) cosubstrate and the Fe(II) cofactor, which are involved in m(6)A oxidative demethylation. In addition, FTO bound to ssRNAs prior to the m(6)A recognition process. Diazirine photocrosslinking contributes to increasing the chances of capturing activated FTO complexes with specific m(6)A recognition and provides new insights into the dynamic FTO oxidative demethylation process.

FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis.

The role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adipogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5'- and 3'-splice sites, spatially overlapping with mRNA splicing regulatory serine/arginine-rich (SR) protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.

Fluorescent peptide indicator displacement assay for monitoring interactions between RNA and RNA binding proteins.

This paper describes a sensitive, non-destructive displacement assay, using a fluorescent peptide indicator, for real-time monitoring of the interactions between RNA and RNA binding proteins (RBPs). The developed fluorescent peptide indicators, each containing a mid-sequence fluorophore unit, allowed sensing of target RNA and RNA-RBP interactions through changes in fluorescence intensity. We anticipate that this assay will open up new possibilities for meaningful studies of RNA-RBP interactions.

A low-molecular-weight supramolecular hydrogel of riboflavin bolaamphiphile for VEGF-siRNA delivery.

A low-molecular-weight hydrogel derived from riboflavin (vitamin B(2)) that self-assembles to provide supramolecular nanofibers, biocompatible material, can be used to deliver VEGF-siRNA efficiently into human cells by the endocytosis pathway, where the siRNA is functionalized.

Femoral head fracture without dislocation by low-energy trauma in a young adult.

We describe the case of a healthy young man with a femoral head fracture by low-energy trauma that occurred without evidence of hip dislocation. While plain radiographs showed no definite fracture or dislocation, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a femoral head fracture with a wedge-shaped cortical depression at the superomedial aspect of the femoral head. Our patient reported feeling that the right hip had been displaced from its joint for a moment. This probably represented subluxation with spontaneous relocation. The characteristic findings and possible mechanisms of this fracture were postulated on the basis of the sequential 3 dimensional-CT and MRI. The clinical results of conservative treatment were better than those of previously reported indentation fractures.

The effects of the 4-(4-Methylpiperazine)phenyl group on nucleosides and oligonucleotides: cellular delivery, detection, and stability.

As drug candidates, one promising way to improve the cellular delivery efficacy of oligonucleotides is to introduce a cationic group. By introducing a cationic moiety into the oligonucleotide structure, they become capable of approaching the cell surface and also of crossing the cellular membrane. In an effort to develop cell-permeable oligonucleotides, we examined the piperazinephenyl-bearing 2'-deoxyuridine ((PP)U), which can be not only cationic but also fluorescent as a cationic monomer for cationic oligonucleotides. Several modified DNA oligonucleotides with different numbers of (PP)U building blocks were synthesized and evaluated for the effect on thermal stability and conformation by the introduction of (PP)U. The cellular delivery of modified oligonucleotides was different depending on the number of (PP)U building blocks. Furthermore, these (PP)U-modified oligonucleotides had sufficient fluorescence that we were able to identify the delivery results without the use of conventional fluorescent tags. They were predominantly localized in the cell cytoplasm. In addition, they were stable enough after 3 hours in the presence of nuclease. These results showed that a piperazinephenyl moiety that is conjugated with nucleobase is able to deliver and detect the oligonucleotides, which suggests that this concept of 'dual-function oligonucleotides' might be utilized in diagnostics, therapeutics, and as a convenient biological tool for probing the activity of oligonucleotides inside cells.

Structural diversity induced by pyrene intercalators in homogeneous oligodeoxyguanylates.

Homogeneous oligodeoxyguanylates incorporating small-molecule intercalator pyrene moieties in a 1,5 relationship form various structures of dimer, trimer, tetramer and internal hairpin form that are yellowish in color because of the intermolecular interactions between the pyrene units.

Probing specific RNA bulge conformations by modified fluorescent nucleosides.

Recently, RNA bulges, three-dimensional structural motifs that function as molecular handles in RNA, were identified in various sequences and have been proposed as the interaction site for RNA-binding drugs. However direct and sensitive monitoring methods specific to RNA bulges have not been well developed. We describe here pyrene-labeled uridine derivatives which were incorporated into HIV TAR RNA bulge sites resulting in greatly enhanced fluorescence, allowing the effective monitoring of base conformations in HIV TAR RNA. To clarify this fluorescence enhancement, Hartree-Fock calculations were performed for natural and pyrene-labeled HIV TAR RNA. The calculated results showed a considerable rotation of the pyrene moiety at U25 due to argininamide-induced conformational changes in the RNA bulge. This simple and efficient method can be used to elucidate conformational changes in specific bulge regions.

Cholesterol-linked pyrene excimer molecular beacon with enhanced cell permeability.

Covelently labeled pyrene excimer molecular beacon (MB) with cholesterol moiety has been developed for enhanced the cellular delivery of MB.(1) Pyrene units were covalently attached into adenosine and incorporated to oligonucleotides at the complementary locations in opposite strands in the middle positions of hairpin stems. The system behaves as an effective MB that changes color from green to blue upon duplex formation. A cholesterol unit was also attached into a free terminus of one of these hairpins. The cholesterol-linked MBs enhanced the cellular delivery of the MBs and showed similar cell permeability to conventional transfection methods. These structurally simple cholesterol-based MB systems, which can be synthesized very efficiently, have good potential for opening up new and exciting opportunities in the field of in vivo biosensors.

Cholesterol-linked fluorescent molecular beacons with enhanced cell permeability.

We appended pyrene units covalently onto adenosine (forming A(P) units) and then incorporated them into oligonucleotides such that they were positioned in complementary locations in opposite strands in the middle positions of hairpin stems. System 1 (A(P)A(P)) behaves as an effective molecular beacon (MB) that changes color from green to blue upon duplex formation. In addition, we attached a cholesterol unit to a free terminus of one of these hairpins; this approach enhanced the cellular delivery of the modified MB relative to those encountered when using conventional transfection methods. These structurally simple cholesterol-based MB systems, which can be synthesized very efficiently, have good potential for opening up new and exciting opportunities in the field of in vivo biosensors.