Single-Molecule Graphene Liquid Cell Electron Microscopy for Instability of Intermediate Amyloid Fibrils.

Single-molecule techniques are powerful microscopy methods that provide new insights into biological processes. Liquid-phase transmission electron microscopy (LP-TEM) is an ideal single-molecule technique for overcoming the poor spatiotemporal resolution of optical approaches. However, single-molecule LP-TEM is limited by several challenges such as electron-beam-induced molecular damage, difficulty in identifying biomolecular species, and a lack of analytical approaches for conformational dynamics. Herein, a single-molecule graphene liquid-cell TEM (GLC-TEM) technique that enables the investigation of real-time structural perturbations of intact amyloid fibrils is presented. It is demonstrated that graphene membranes significantly extend the observation period of native amyloid beta proteins without causing oxidative damage owing to electron beams, which is necessary for imaging. Stochastic and time-resolved investigations of single fibrils reveal that structural perturbations in the early fibrillar stage are responsible for the formation of various amyloid polymorphs. The advantage of observing structural behavior in real time with unprecedented resolution will potentially make GLC-TEM a complementary approach to other single-molecule techniques.

Re-Emergence of HMPV in Gwangju, South Korea, after the COVID-19 Pandemic.

The non-pharmaceutical interventions implemented to prevent the spread of COVID-19 have affected the epidemiology of other respiratory viruses. In South Korea, Human metapneumovirus (HMPV) typically occurs from winter to the following spring; however, it was not detected for two years during the COVID-19 pandemic and re-emerged in the fall of 2022, which is a non-epidemic season. To examine the molecular genetic characteristics of HMPV before and after the COVID-19 pandemic, we analyzed 427 HMPV-positive samples collected in the Gwangju area from 2018 to 2022. Among these, 24 samples were subjected to whole-genome sequencing. Compared to the period before the COVID-19 pandemic, the incidence rate of HMPV in 2022 increased by 2.5-fold. Especially in the age group of 6-10 years, the incidence rate increased by more than 4.5-fold. In the phylogenetic analysis results, before the COVID-19 pandemic, the A2.2.2 lineage was predominant, while in 2022, the A2.2.1 and B2 lineage were observed. The non-pharmaceutical interventions implemented after COVID-19, such as social distancing, have reduced opportunities for exposure to HMPV, subsequently leading to decreased acquisition of immunity. As a result, HMPV occurred during non-epidemic seasons, influencing the age distribution of its occurrences.

Effects of suprahyoid muscle strengthening exercise using kinesiology taping on muscle activation and thickness in community-dwelling elderly: A randomized controlled trial.

BACKGROUND: Recently, swallowing resistive exercise using kinesiology taping (KT) has been reported as a novel method for dysphagia rehabilitation However, clinical evidence is still unclear, and effects in the elderly have not been confirmed. OBJECTIVE: This study aimed to investigate the effects of suprahyoid muscle strengthening exercise using KT on muscle activation and thickness in community-dwelling elderly. METHODS: A total of 24 healthy older people were enrolled in this study and randomly assigned to an experimental group and a placebo group. In the experimental group, KT was attached to the front of the neck with a tension of about 70% to 80%, and a resistive swallowing exercise was performed. In the placebo group, the tape was applied similarly but without tension. Both groups performed resistive swallowing exercises 10 times a day (50 swallows per day) for 6 weeks. The activation and thickness of the suprahyoid muscles were measured using portable ultrasound equipment and an surface electromyelograph device. RESULTS: The experimental group showed a significant increase in suprahyoid muscle activation (mean and peak) and muscle thickness (digastric and mylohyoid) than the placebo group (all, P < .05). CONCLUSION: This study confirmed that suprahyoid muscle strengthening exercise using KT had a positive effect on the suprahyoid muscles in healthy older adults, thus suggesting the possibility of a therapeutic exercise method for dysphagia rehabilitation.

Shaving Papillary Thyroid Carcinoma Involving Functioning Recurrent Laryngeal Nerve: Safety of Incomplete Tumor Resection and Nerve Sparing.

BACKGROUND: Whether to sacrifice or spare the recurrent laryngeal nerve (RLN) when papillary thyroid carcinoma (PTC) involves a functioning RLN remains controversial. Oncological outcomes after shaving PTC with gross remnant on the RLN have been rarely reported. The objective of this study was to evaluate the oncological outcomes of patients who underwent shaving of a PTC from the RLN, leaving a gross residual tumor with the intent of vocal function preservation. METHODS: A retrospective, cohort study was conducted in 47 patients who were determined to have PTC invasion of the RLN via intraoperative inspection and underwent tumor shaving with macroscopic remnant (R2 resection) less than 1 cm in length and 4 mm in thickness. Median follow-up period was 93 (range, 60-215) months. The primary endpoint was the recurrence-free survival and the progression-free survival. Secondary endpoints were biochemical outcomes (serum thyroglobulin) and vocal cord function. RESULTS: Of the 47 patients, five (10.6%) patients showed recurrence (central neck, 3; lateral neck, 2) without death or distant metastasis. The RLN was resected along with the tumor in one (2.1%) patient who presented with progression of the residual tumor. Postoperative temporary vocal cord paralysis occurred in six (12.8%) patients without permanent cases. The final nonstimulated serum thyroglobulin was 0.7 ± 1.8 ng/ml. CONCLUSIONS: Shaving a tumor from a RLN with gross residual disease may be considered an alternative strategy to preserve vocal function when complete tumor resection with nerve preservation is impossible in patients with PTC invading a functioning RLN.

Occupational therapists views on addressing the sexuality of adult clients in rehabilitation settings: A qualitative focus group study.

Sexuality is a common concern among people with disabilities or chronic conditions, and failure to address sexuality can lead to poorer rehabilitation outcomes. To explore the factors affecting addressing the sexuality of adult clients in clinical practice as perceived by Korean Occupational Therapists (OTs) and the perspective on what needs to be established to address sexuality in occupational therapy practice. This descriptive qualitative study using focus group interviews was conducted with 15 OTs providing rehabilitation services for adult clients in the post-onset maintenance phase or for outpatients in Seoul, South Korea. Data collected through focus groups were analyzed using the constant comparative method. The main factors influencing addressing clients sexuality in clinical practice were identified: "absence of institutional system for addressing sexuality in rehabilitation setting" for environmental factors; "lack of professional competency" for therapist-related factors; and "repressed sexuality" for client-related factors. Moreover, recognizing that "sexual health is one of the goals of rehabilitation" and prioritizing it in rehabilitation settings are essential. OTs must be "experts with knowledge and skills" to access the client's sexuality, and "education and publicity" should be actively conducted to raise awareness of sexual health for clients. To deal with clients sexuality, institutional preparation should be prioritized under the recognition that sexual health is one of the goals of rehabilitation. In addition, it is necessary to prepare a relevant curriculum for OTs and create awareness so that clients can recognize improving sexual activity as a role of OTs.

Kinesiology taping and ankle foot orthosis equivalent therapeutic effects on gait function in stroke patients with foot drop: A preliminary study.

An ankle foot orthosis (AFO) is a standard type of orthosis applied to immediately treat foot drop symptoms. Kinesiology taping (KT) is a therapeutic method used in patients with neurological diseases, such as stroke, as well as in patients after orthopedic and sports injuries. This study aimed to compare outcomes of AFO treatment with those of KT to investigate the effect on gait ability in patients with foot drop after stroke. We recruited 18 patients exhibiting foot drop from stroke. Gait ability was assessed under 2 conditions: treatment with KT and that with AFO using the GAITRite system according to the following parameters: cadence, velocity, swing time, stance time, step length, and stride length. As a result, gait ability after treatment with KT and that after treatment with AFO showed no significant differences in cadence (P = .851), velocity (P = .865), swing time (P = .289 and .123), stance time (P = .255 and .711), step length (P = .955 and .975), and stride length (P = .711 and .690) of the affected and less-affected limbs. This study demonstrated that KT and AFO use have similar effects on gait function in patients with foot drop after stroke. Thus, treatment of foot drop with KT may be an alternative in patients for whom AFO use is contraindicated.

Chin-tuck assistant system (CAS)-A novel method using auditory feedback for postural maintenance in a chin-tuck maneuver: A randomized trial.

INTRODUCTION: Chin-tuck are effective in patients with dysphagia, where aspiration can occur due to pharyngeal swallowing delays. This study aims to verify whether Chin-tuck Assistant System Maneuver (CAS-M) supplemented with Chin-Tuck Maneuver (CTM) is effective for learning and maintaining correct chin-tuck postures. In addition, we investigated the possibility of using CAS-M as a customized rehabilitation treatment program for patients with poor cognitive ability, attention issues, and general swallowing disorders. INTERVENTION: To demonstrate the effectiveness of CAS, we recruited 52 healthy adults and assigned them to 2 groups. The CTM group was trained to maintain the correct chin-tuck posture using the general Chin-Tuck Maneuver, while the CAS-M group was trained using CAS. Four evaluations were conducted using CAS to investigate the degree of postural maintenance of chin-tuck before and after intervention. RESULTS: The CAS-M group showed a statistically significant difference in TIME, BEEP, and change (P < .05), but the CTM group showed no statistically significant differences (P < .05). YZ evaluation showed no statistically significant differences in both groups. CONCLUSION: After examining the effects of CAS-M using CAS on healthy adults, we confirmed this to be a more effective method for correct chin-tuck posture than conventional CTM.

Viral detection from negative mumps cases with respiratory symptoms in Gwangju, South Korea in 2021.

Mumps is the second-most reported infectious disease in South Korea; however, due to the low pathogen confirmation rate in laboratory diagnoses, we proposed a method for reevaluating the high incidence rate via the laboratory verification of other viral diseases. In 2021, 63 cases of pharyngeal or cheek mucosal swabs of suspected mumps cases in Gwangju, South Korea, were assessed for causative pathogens using massive simultaneous pathogen testing. More than one respiratory virus was detected in 60 cases (95.2%), 44 (73.3%) of which were codetected. Human rhinovirus was detected in 47 cases, followed by human herpesvirus (HHV)6 in 30; HHV4 (17), human bocavirus (17), HHV5 (10), and human parainfluenza virus 3 (6) were also detected. Our findings suggest the need for further investigations on the pathogenesis of diseases mimicking mumps, which are considered to aid with appropriate public health responses, treatment, and the prevention of infectious disease outbreaks.

Synthesis of a New Glycoconjugate with Di-á´ -Psicose Anhydride Structure.

Demand for healthy diets has led researchers to explore new saccharide as sucrose alternatives. ᴅ-Psicose, the C-3 epimer of ᴅ-fructose, has a similar sweetness intensity to sucrose but contributes fewer calories. This study proposes a disaccharide with a stable structure derived from ᴅ-psicose. The compound with a spiro-tricyclic core was generated at 32% conversion via caramelization of ᴅ-psicose under acidic anhydrous conditions. The compound was identified by high-resolution mass spectrometry and multi-dimensional nuclear magnetic resonance (NMR). The molecular formula was established as C12H20O10 from the molecular weight of m/z 324.1055. Twelve signals were observed by the 13C NMR spectrum. This compound, denoted di-ᴅ-psicose anhydride (DPA), exhibited a lower water solubility (40 g/L) and higher thermal stability (peak temperature = 194.7 °C) than that of ᴅ-psicose (peak temperature = 126.5 °C). The quantitatively evaluated metal ion scavenging ability of DPA was the best in magnesium (average 98.6 ± 1.1%). This synthesis methodology can provide disaccharides with high stability-reducing heavy metals.

Reactogenicity and Immunogenicity of the ChAdOx1 nCOV-19 Coronavirus Disease 2019 Vaccine in South Korean Healthcare Workers.

PURPOSE: The association between reactogenicity and immunogenicity of the ChAdOx1 nCOV-19 is controversial. We aimed to evaluate this association among South Korean healthcare workers (HCWs). MATERIALS AND METHODS: Participants received two doses of the ChAdOx1vaccine 12 weeks apart. Blood samples were tested for anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike protein receptor binding domain antibodies about 2 months after the first and second doses using the Elecsys Anti-SARS-CoV-2 S assay kits. Adverse events were noted using an online self-reporting questionnaire. RESULTS: Among the 232 HCWs, pain (85.78% after the first dose vs. 58.62% after the second dose, p<0.001) was the most prominent local reaction, and myalgia or fatigue (84.05% vs. 53.02%, p<0.001) was the most prominent systemic reaction. The frequency of all adverse events was significantly reduced after the second dose. After the first dose, the anti-SARS-CoV-2 S showed significantly higher titer in the group with swelling, itching, fever, and nausea. Also, the anti-SARS-CoV-2 S titer significantly increased as the grade of fever (p=0.007) and duration of fever (p=0.026) increased; however, there was no significant correlation between immunogenicity and adverse event after the second dose. The group with pain after the first dose showed a greater increase in the anti-SARS-CoV-2 S difference between the second and first doses compared to the group without pain (542.2 U/mL vs. 363.8 U/mL, p=0.037). CONCLUSION: The frequency of adverse events occurring after the first dose of the ChAdOx1 was significantly reduced after the second dose. Interestingly, the elevation of anti-SARS-CoV-2 S titer was significantly increased in the group with pain after the first dose.

Universal assembly of liquid metal particles in polymers enables elastic printed circuit board.

An elastic printed circuit board (E-PCB) is a conductive framework used for the facile assembly of system-level stretchable electronics. E-PCBs require elastic conductors that have high conductivity, high stretchability, tough adhesion to various components, and imperceptible resistance changes even under large strain. We present a liquid metal particle network (LMPNet) assembled by applying an acoustic field to a solid-state insulating liquid metal particle composite as the elastic conductor. The LMPNet conductor satisfies all the aforementioned requirements and enables the fabrication of a multilayered high-density E-PCB, in which numerous electronic components are intimately integrated to create highly stretchable skin electronics. Furthermore, we could generate the LMPNet in various polymer matrices, including hydrogels, self-healing elastomers, and photoresists, thus showing their potential for use in soft electronics.

Ground-Reaction-Force-Based Gait Analysis and Its Application to Gait Disorder Assessment: New Indices for Quantifying Walking Behavior.

Gait assessment is an important tool for determining whether a person has a gait disorder. Existing gait analysis studies have a high error rate due to the heel-contact-event-based technique. Our goals were to overcome the shortcomings of existing gait analysis techniques and to develop more objective indices for assessing gait disorders. This paper proposes a method for assessing gait disorders via the observation of changes in the center of pressure (COP) in the medial-lateral direction, i.e., COPx, during the gait cycle. The data for the COPx were used to design a gait cycle estimation method applicable to patients with gait disorders. A polar gaitogram was drawn using the gait cycle and COPx data. The difference between the areas inside the two closed curves in the polar gaitogram, area ratio index (ARI), and the slope of the tangential line common to the two closed curves were proposed as gait analysis indices. An experimental study was conducted to verify that these two indices can be used to differentiate between stroke patients and healthy adults. The findings indicated the potential of using the proposed polar gaitogram and indices to develop and apply wearable devices to assess gait disorders.

Effect of Peripheral Magnetic Stimulation for Dysphagia Rehabilitation: A Systematic Review.

Recently, a therapeutic method to stimulate the suprahyoid muscle using peripheral magnetic stimulation for dysphagia rehabilitation has been reported. However, clinical evidence, application protocol, and intervention method remain unclear. Therefore, a systematic review of the published literature is needed. The objective of this study was to systematically review clinical studies of peripheral magnetic stimulation applied for rehabilitation of dysphagia. Issues to be considered in future studies are also suggested. This systematic review performed a literature search of four databases (Medline, Embase, CINAHL, and Web of Science) to identify relevant studies published on the application of repetitive peripheral magnetic stimulation (rPMS) for swallowing-related muscles between 2010 and 2022. Seven studies were reviewed. Randomized controlled trials and one-group pre-post, case study designs were included. In the included studies, rPMS was applied to strengthen the submental suprahyoid muscles. The intervention regime varied. The rPMS was applied at a frequency of 30 Hz for 2 s. Rest time ranged from 8 s to 27-28 s. The number of intervention sessions ranged from 2-3 to 30. The intensity ranged from pain-inducing minimum intensity (90% of maximum stimulus output) to non-painful intensity (70-80% of maximum intensity). The rPMS on the suprahyoid muscles had positive effects on physiological changes in the swallowing function, such as displacement of the hyoid bone, muscle strength (cervical flexor, jaw-opening force), swallowing safety, swallowing performance, and swallowing-related quality of life. Participants also reported little pain and adverse reactions during rPMS. Although rPMS is a therapeutic option that can help improve the swallowing function as a non-invasive stimulation method in the rehabilitation of dysphagia, clinical evidence is needed for the development of clear stimulation protocols and guidelines.

Characteristics of plaque lipid-associated macrophages and their possible roles in the pathogenesis of atherosclerosis.

PURPOSE OF REVIEW: Recent findings from single-cell transcriptomic studies prompted us to revisit the role of plaque foamy macrophages in the pathogenesis of atherosclerosis. In this review, we compared the gene expression profile of plaque foamy macrophages with those of other disease-associated macrophages and discussed their functions in the pathogenesis of atherosclerosis. RECENT FINDINGS: To understand the phenotypes of macrophages in atherosclerotic aorta, many research groups performed single-cell RNA sequencing analysis and found that there are distinct phenotypic differences among intimal foamy, nonfoamy and adventitial macrophages. Especially, the plaque foamy macrophages express triggering receptor expressed on myeloid cells 2 (TREM2), a key common feature of disease-associated macrophages in Alzheimer's disease, obesity, cirrhosis and nonalcoholic steatohepatitis. These TREM2 + macrophages seem to be protective against chronic inflammation. SUMMARY: As the gene expression profile of plaque foamy macrophages is highly comparable to that of lipid-associated macrophages from obesity, we named the plaque foamy macrophages as plaque lipid-associated macrophages (PLAMs). PLAMs have a high level of gene expression related to phago/endocytosis, lysosome, lipid metabolism and oxidative phosphorylation. Considering the protective function of lipid-associated macrophages against adipose tissue inflammation, PLAMs may suppress atherosclerotic inflammation by removing modified lipids and cell debris in the plaque.

Structure-based inhibitor design for reshaping bacterial morphology.

The spiral shape of intestinal pathogen Campylobacter jejuni is critical for invasion of intestinal mucosa epithelial cells. Insofar as this cell morphology plays a role in the pathology of C. jejuni infection, its restructuring by pharmacological intervention could be an unexplored means to prevention of infection. We recently described that peptidoglycan hydrolase 3 (Pgp3) is involved in the spiral-shape formation of C. jejuni. We report herein the design and synthesis of the hydroxamate-based inhibitors targeting Pgp3. C. jejuni cells exposed to these inhibitors changed from the helical- to rod-shaped morphology, comparable to the case of the pgp3-deletion mutant. Evidence for the mechanism of action was provided by crystal structures of Pgp3 in complex with inhibitors, shedding light into the binding modes of inhibitors within the active site, supported by kinetics and molecular-dynamics simulations. C. jejuni exposed to these inhibitors underwent the morphological change from helical- to rod-shaped bacteria, an event that reduce the ability for invasion of the host cells. This proof of concept suggests that alteration of morphology affects the interference with the bacterial infection.

Determination of Residual Triflumezopyrim Insecticide in Agricultural Products through a Modified QuEChERS Method.

A rapid and simple analytical method for triflumezopyrim, a new class of mesoionic insecticides and commercialized molecules from DuPont, was developed with a modified QuEChERS method. The pH adjustment was used to improve the extraction efficiency of acetonitrile solvent, and dispersive solid-phase extraction was employed for the clean-up process. The five selected food commodities were used to verify the present optimized method, which displayed good linearity with an excellent correlation coefficient (R2 = 0.9992-0.9998) in the 0.003-0.30 mg/kg calibration range. The method limits of detection (LOD) and quantification (LOQ) were determined to be a value of 0.003 and 0.01 mg/kg, respectively. The mean recovery for the triflumezopyrim was in the 89.7-104.3% range. The relative standard deviations were ≤9.8% for intra- (n = 5) and inter-day (n = 15) precisions at concentrations of 0.01, 0.1, and 0.5 mg/kg in the five representative samples. The matrix effect has been calculated to confirm the effect during ionization of the analyte in the UPLC-MS/MS. The matrix effects of the instrumental analysis showed that triflumezopyrim was less susceptible to matrices. The proposed analytical method in this study has effectively improved the accuracy, selectivity, and sensitivity for the determination of triflumezopyrim in agricultural commodities; therefore, it can serve as a reference method for the establishment of maximum residue limits (MRLs).

Effects of Semi-Immersive Virtual Reality-Based Cognitive Training Combined with Locomotor Activity on Cognitive Function and Gait Ability in Community-Dwelling Older Adults.

This study aimed to investigate the effects of semi-immersive virtual reality-based cognitive training (VRCT) combined with locomotor activity on cognitive function, balance, and gait ability in older adults. Eighteen community-dwelling older adults participated in this study. Subjects who met the selection criteria were assigned to an experimental group (n = 9) and a control group (n = 9). The experimental group received VRCT combined with locomotor activity for 30 min a day, three times a week, for 6 weeks. The control group received tabletop activity-based cognitive training for the same amount of time. Before and after the training, the Korean Mini-Mental State Examination (K-MMSE), Trail Making Test (TMT; A and B), and Digit Span Test (DST; forward and backward) were used to evaluate cognitive function; and the Timed Up and Go (TUG) test and 10-m Walking Test (10MWT) were used to evaluate the improvement in the balance and gait ability parameters. After the intervention, the experimental group showed a significantly greater improvement in the TMT-A (p = 0.045) and DST-backward (p = 0.012) scores compared with the control group. Regarding the gait ability variable, the experimental group showed a significant improvement in the 10MWT test (p = 0.001). This study confirmed that semi-immersive VRCT combined with locomotor activity is useful for improving cognitive function and gait ability in older adults. Therefore, VRCT combined with locomotor activity can be used as a simultaneous intervention for cognitive rehabilitation and functional capacity improvement in older adults.

Inhibition of soluble epoxide hydrolase by phytochemical constituents of the root bark of Ulmus davidiana var. japonica.

A novel compound 1 and nine known compounds (2-10) were isolated by open column chromatography analysis of the root bark of Ulmus davidiana. Pure compounds (1-10) were tested in vitro to determine the inhibitory activity of the catalytic reaction of soluble epoxide hydrolase (sEH). Compounds 1, 2, 4, 6-8, and 10 had IC50 values ranging from 11.4 ± 2.3 to 36.9 ± 2.6 µM. We used molecular docking to simulate inhibitor binding of each compound and estimated the binding pose of the catalytic site of sEH. From this analysis, the compound 2 was revealed to be a potential inhibitor of sEH in vitro and in silico. Additionally, molecular dynamics (MD) study was performed to find detailed interaction signals of inhibitor 2 with enzyme. Finally, compound 2 is promising candidates for the development of a new sEH inhibitor from natural plants.

Chin tuck against resistance exercise for dysphagia rehabilitation: A systematic review.

BACKGROUND: Chin tuck against resistance (CTAR) exercise has been recently reported to be a new therapeutic exercise method that can help improve swallowing function in patients with dysphagia. However, due to the differences in exercise protocols, methods and the tools used across studies of CTAR exercise, an overall systematic review of these studies is necessary. OBJECTIVE: The present study investigated the exercise protocols, methods and tools used in various studies of CTAR exercise and summarised their findings. METHODS: We searched for studies related to CTAR exercise using electronic databases and selected nine articles for review. The articles were categorised on the basis of four criteria: study design and quality, training protocol, outcome measures and clinical effect. RESULTS: Four articles reported that CTAR exercise not only helped activate the suprahyoid muscle in healthy adults, but also activated the sternocleidomastoid muscle less than Shaker exercise. In addition, five articles reported that CTAR exercise was effective in improving swallowing function and oral diet stage in the pharyngeal phase, including reduction of airway aspiration in patients with dysphagia after stroke. CONCLUSIONS: CTAR exercise more selectively activates the suprahyoid muscle and is an effective therapeutic exercise for improving swallowing function in patients with dysphagia. Because it is less strenuous than Shaker exercise, it requires less physical burden and effort, allowing greater compliance.