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Abstract The Alpha stent is an intracranial closed-cell stent with a unique mesh design to enhance wall apposition. It recently underwent structural modifications to facilitate easier stent deployment. This study aimed to evaluate the safety and efficacy of stent-assisted coil embolization for unruptured intracranial aneurysms using the Alpha stent. Between January 2021 and November 2021, 35 adult patients with 35 unruptured intracranial aneurysms in the distal internal carotid artery were prospectively enrolled. For efficacy outcomes, magnetic resonance angiography at the 6-month follow-up was evaluated using the Raymond-Roy occlusion classification (RROC). The safety outcome evaluated the occurrence of symptomatic procedure-related neurological complications up to 6 months postoperatively. Technical success was achieved in 34/35 (97.1%). Six months postoperatively, aneurysm occlusion showed RROC I in 32/35 (91.4%) and RROC II in 3/35 (8.6%) patients. Procedure-related neurologic complications occurred in one patient (2.9%) who experienced hemiparesis due to acute lacunar infarction, which resulted in a 6-month mRS score of 1. The Alpha stent demonstrated excellent efficacy and safety outcomes in stent-assisted coil embolization of unruptured distal ICA aneurysms. The recent structural modifications allowed for easier stent delivery and deployment. Clinical trial registration number: KCT0005841; registration date: 28/01/2021.

Abstract Astrocytes are involved in various processes in the central nervous system (CNS). As the most abundant cell type in the CNS, astrocytes play an essential role in neuronal maintenance and support, synaptic activity, neuronal metabolism, and amyloid-beta (Aβ) clearance. Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral impairment. The transformation of astrocytes is involved in various neurodegenerative diseases, such as AD. Since astrocytes have functional diversity and morphological and physiological heterogeneity in the CNS, AD-related astrocytes might show various pathological phenotypes during AD. Astrocytes developing pathological phenotypes could contribute to AD progression. In this review, we provide an overview of the pathological phenotypes of astrocytes in the context of AD, highlighting recent findings in human and mouse AD.

Adenylate kinase is a ubiquitous enzyme in living systems and undergoes dramatic conformational changes during its catalytic cycle. For these reasons, it is widely studied by genetic, biochemical, and biophysical methods, both experimental and theoretical. We have determined the basic crystal structures of three differently liganded states of adenylate kinase from Methanotorrus igneus, a hyperthermophilic organism whose adenylate kinase is a homotrimeric oligomer. The multiple copies of each protomer in the asymmetric unit of the crystal provide a unique opportunity to study the variation in the structure and were further analyzed using advanced crystallographic refinement methods and analysis tools to reveal conformational heterogeneity and, thus, implied dynamic behaviors in the catalytic cycle.

Neuroinflammation and oxidative stress have been implicated in the pathogenesis of Alzheimer’s disease (AD). Neuroinflammation and oxidative stress are associated with neuronal death in AD. Astrocytes are linked to neuroinflammation during AD. Astrocytes are important contributors to AD progression. Although the role of thioredoxin-interacting protein (TXNIP) has been identified in inflammation and oxidative stress, the mechanism by which TXNIP regulates inflammation and oxidative stress in astrocytes during AD remains unclear. In the present study, we found that TXNIP gene levels were elevated in cerebral cortex of patients with AD. The protein levels of TXNIP were elevated in GFAP-positive astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD. Our results showed that TXNIP increased expression of genes related to pro-inflammatory reactive astrocytes and pro-inflammatory cytokines and chemokines in human astrocytes. Moreover, TXNIP increased production of pro-inflammatory cytokines and chemokines in human astrocytes. TXNIP induced activation of NK-kB signaling and over-production of mitochondrial reactive oxygen species (mtROS) in human astrocytes. TXNIP also induced mitochondrial oxidative stress by reduction of mitochondrial respiration and ATP production in human astrocytes. Furthermore, elevated TXNIP levels are correlated with caspase-3 activation of GFAP-positive astrocytes in patients with AD and mouse AD. TXNIP induced mitochondria-dependent apoptosis via caspase-9 and caspase-3 activation in human astrocytes. These results suggest that TXNIP contributes to induction of pro-inflammatory phenotype and caspase-3 activation in astrocytes during AD.

Abstract In many soft sensor systems, external wires for connecting the sensors to control circuits have posed practical problems, in terms of compact form factors and physical robustness. This study proposes a design of soft sensor arrays that can operate with a drastically reduced number of wires without degrading the original performance. The proposed concept is an array of soft sensing modules, each of which consists of an inductor and a capacitor embedded next to the resistive sensing module, constructing a resistor-inductor-capacitor band-pass filter. By adjusting the values of the capacitance and the inductance, unique frequency band is assigned to each sensing module, enabling the distinctive detection using only two external wires regardless of the number of modules. The multi-touch sensing functionality of the system is analytically modeled and experimentally characterized. Taking advantage of the design, a fingertip tactile sensor and an insole foot pressure sensor are demonstrated as practical applications.

PurposeThis study aimed to discover electrophysiologic markers correlated with clinical responses to vigabatrin-based treatment in infants with epileptic spasms (ES).MethodThe study involved a descriptive analysis of ES patients from a single institution, as well as electroencephalogram (EEG) analyses of 40 samples and 20 age-matched healthy infants. EEG data were acquired during the interictal sleep state prior to the standard treatment. The weighted phase-lag index (wPLI) functional connectivity was explored across frequency and spatial domains, correlating these results with clinical features.ResultsInfants with ES exhibited diffuse increases in delta and theta power, differing from healthy controls. For the wPLI analysis, ES subjects exhibited higher global connectivity compared to control subjects. Subjects who responded favorably to treatment were characterized by higher beta connectivity in the parieto-occipital regions, while those with poorer outcomes exhibited lower alpha connectivity in the frontal regions. Individuals with structural neuroimaging abnormalities exhibited correspondingly low functional connectivity, implying that ES patients who maintain adequate structural and functional integrity are more likely to respond favorably to vigabatrin-based treatments.ConclusionThis study highlights the potential utility of EEG functional connectivity analysis in predicting early response to treatments in infants with ES.

BackgroundMental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20–40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited.MethodsIn this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001.ResultsThe patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = −6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = −7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = −5.02 and −5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group.ConclusionHere, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue.

(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization.

Background and Objectives: Patients recovering from mild coronavirus disease (COVID-19) reportedly have dysphagia or difficulty in swallowing. We compared the prevalence of dysphagia between patients diagnosed with mild COVID-19 and those diagnosed with aspiration pneumonia alone. Materials and Methods: A retrospective study was conducted from January 2020 to June 2023 in 160 patients referred for a videofluoroscopic swallowing study (VFSS) to assess for dysphagia. The cohort included 24 patients with mild COVID-19 and aspiration pneumonia, 30 with mild COVID-19 without aspiration pneumonia, and 106 with aspiration pneumonia alone. We reviewed the demographic data, comorbidities, and VFSS results using the penetration–aspiration scale (PAS) and functional dysphagia scale (FDS). Results: In a study comparing patients with mild COVID-19 (Group A) and those with aspiration pneumonia alone (Group B), no significant differences were observed in the baseline characteristics, including the prevalence of dysphagia-related comorbidities between the groups. Group A showed milder dysphagia, as evidenced by lower PAS and FDS scores, shorter oral and pharyngeal transit times (p = 0.001 and p = 0.003, respectively), and fewer residues in the vallecula and pyriform sinuses (p < 0.001 and p < 0.03, respectively). When Group A was subdivided into those with COVID-19 with (Group A1) and without aspiration pneumonia (Group A2), both subgroups outperformed Group B in terms of specific VFSS metrics, such as oral transit time (p = 0.01), pharyngeal transit time (p = 0.04 and p = 0.02, respectively), and residue in the vallecula (p = 0.04 and p = 0.02, respectively). However, Group B showed improved triggering of the pharyngeal swallowing reflex compared with Group A2 (p = 0.02). Conclusion: Mild COVID-19 patients showed less severe dysphagia than those with aspiration pneumonia alone. This finding was consistent across VFSS parameters, even when the COVID-19 group was subdivided based on the status of aspiration pneumonia.

BackgroundAlthough psychological interventions for stress relief, such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR), have been developed, they have not been widely used in treating depression. The use of mobile devices can increase the possibility of actual use by integrating interventions and reducing the difficulty and cost burden of treatment application. This study aims to determine whether “inMind,” an integrated mobile application for stress reduction, developed for the general population, decreases stress for patients with mild to moderate major depressive disorder during the pharmacological treatment period.MethodsThis study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in Republic of Korea, provides integrated interventions for stress reduction for the general population through three modules based on mindfulness-based stress reduction, cognitive behavior therapy, and relaxation sounds that are known to be effective in stress reduction (“meditation,” “cognitive approach,” and “relaxation sounds,” respectively). Participants (n = 215) recruited via medical practitioner referral will be randomized to an App first group (fAPP) or a wait list crossover group (dAPP). The study will be conducted over 8 weeks; the fAPP group will use the App for the first 4 weeks and the dAPP group for the next 4 weeks. During all study periods, participants will receive their usual pharmacological treatment. The Depression Anxiety Stress Scale-21 is the primary outcome measure. The analysis will employ repeated measurements using a mixed-model approach.DiscussionThe App can potentially be an important addition to depression treatment because of its applicability and the comprehensive nature of the interventions that covers diverse stress-relieving models.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585.

Aging leads to time-dependent functional decline of all major organs. In particular, the aging brain is prone to cognitive decline and several neurodegenerative diseases. Various studies have attempted to understand the aging process and underlying molecular mechanisms by monitoring changes in gene expression in the aging mouse brain using high-throughput sequencing techniques. However, the effect of microRNA (miRNA) on the post-transcriptional regulation of gene expression has not yet been comprehensively investigated. In this study, we performed global analysis of mRNA and miRNA expression simultaneously in the hypothalamus and hippocampus of young and aged mice. We identified aging-dependent differentially expressed genes, most of which were specific either to the hypothalamus or hippocampus. However, genes related to immune response-related pathways were enriched in upregulated differentially expressed genes, whereas genes related to metabolism-related pathways were enriched in downregulated differentially expressed genes in both regions of the aging brain. Furthermore, we identified many differentially expressed miRNAs, including three that were upregulated and three that were downregulated in both the hypothalamus and hippocampus. The two downregulated miRNAs, miR-322-3p, miR-542-3p, and the upregulated protein-encoding coding gene C4b form a regulatory network involved in complement and coagulation cascade pathways in the hypothalamus and hippocampus of the aging brain. These results advance our understanding of the miRNA-mediated gene regulatory network and its influence on signaling pathways in the hypothalamus and hippocampus of the aging mouse brain.

IntroductionRecurrences and diagnostic instability of panic disorder (PD) are common and have a negative effect on its long-term course. Developing a novel assessment tool for anxiety that can be used in a multimodal approach may improve these problems in panic disorder patients. This study assessed the feasibility of virtual reality-based assessment in panic disorder (VRA-PD).MethodsTwenty-five patients with PD (ANX group) and 28 healthy adults (CON group) participated in the study. VRA-PD consisted of four modules based on the key components of cognitive behavior therapy for an anxiety disorder: “Baseline evaluation module” (M0), “Daily environment exposure module” (M1), “Relaxation module” (M2), and “Interoceptive exposure module” (M3). Multiple evaluations, including self-rating anxiety scores (AS) and physiological responses [heart rate variability (HRV) index], were performed in three steps at M1, M2, and M3, and once at M0. Comparisons between patients with PD and healthy controls, factor analysis of variables in VRA-PD, changes in responses within modules, and correlation analysis between variables in VRA-PD and anxiety symptoms assessed by psychological scales were performed.ResultsAll participants completed the VRA-PD without discontinuation. The ANX group reported significantly higher AS for all steps and a smaller HRV index in M1 (steps 1 and 2) and M2 (step 1). Repeated-measures analysis of covariance (ANCOVA) revealed significant interaction effects for AS in M1 (F = 4.09, p = 0.02) and M2 (F = 4.20, p = 0.02), and HRV index in M2 (F = 16.22, p < 0.001) and M3 (F = 21.22, p = 0.02). The HRV index only indicated a good model fit for the three-factor model, reflecting the construct of the VRA-PD. Both AS and HRV indexes were significantly correlated with anxiety and depression symptoms.DiscussionThe current study provides preliminary evidence that the VRA-PD could be a valid anxiety behavior assessment tool.

Abstract Background An open‐label single‐arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma. Methods Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Levetiracetam was given at 1,000–2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6‐month progression‐free survival (6mo‐PFS) and 24‐month overall survival (24mo‐OS), respectively. Outcomes of the study group were compared to those of an external control group. Results Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo‐PFS, 84.9% vs. 72.3%, p = 0.038; 24mo‐OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score‐matched analysis (6mo‐PFS, 88.0% vs. 76.9%, p = 0.071; 24mo‐OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam. Conclusions The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted.

Abstract A new concept of read-out method for ferroelectric random-access memory (FeRAM) using a graphene layer as the channel material of bottom-gated field effect transistor structure is demonstrated experimentally. The transconductance of the graphene channel is found to change its sign depending on the direction of spontaneous polarization (SP) in the underlying ferroelectric layer. This indicates that the memory state of FeRAM, specified by the SP direction of the ferroelectric layer, can be sensed unambiguously with transconductance measurements. With the proposed read-out method, it is possible to construct an array of ferroelectric memory cells in the form of a cross-point structure where the transconductance of a crossing cell can be measured selectively without any additional selector. This type of FeRAM can be a plausible solution for fabricating high speed, ultra-low power, long lifetime, and high density 3D stackable non-volatile memory.

Abstract Self-talk can improve cognitive performance, but the underlying mechanism of such improvement has not been investigated. This study aimed to elucidate the effects of self-talks on functional connectivity associated with cognitive performance. We used the short form of Progressive Matrices Test (sRPM) to measure differences in performance improvements between self-respect and self-criticism. Participants were scanned using functional magnetic resonance imaging in the following order: baseline, during-sRPM1, post-sRPM1, self-respect or self-criticism, during-sRPM2, and post-sRPM2. Analysis was conducted to identify the self-talks' modulatory effects on the reward-motivation, default mode, and central-executive networks. Increase in sRPM2 score compared to sRPM1 score was observed only after self-criticism. The self-talk-by-repetition interaction effect was not found for during-sRPM, but found for post-sRPM; decreased nucleus accumbens-based connectivity was shown after self-criticism compared with self-respect. However, the significant correlations between the connectivity change and performance change appeared only in the self-respect group. Our findings showed that positive self-talk and negative self-talk differently modulate brain states concerning cognitive performance. Self-respect may have both positive and negative effects due to enhanced executive functions and inaccurate confidence, respectively, whereas self-criticism may positively affect cognitive performance by inducing a less confident state that increases internal motivation and attention.

ObjectiveA lack of understanding of the clinical course of neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) often complicates the decision-making in terms of optimal timing and mode of treatment. We investigated the outcomes of stereotactic radiosurgery (SRS) in this population.MethodsWe retrospectively analyzed NF2 patients treated with Gamma-Knife SRS for VS in our tertiary referral center. A total of 41 treated lesions from 33 patients were collected with a follow-up period of 69.1 (45.0-104.8) months. We reviewed the treatment history, hearing function, and other treatment-related morbidities in individual cases. We also analyzed pre- and post-treatment tumor volumes via imaging studies. Longitudinal volumetric analyses were conducted for the tumor volume response of the 41 treated lesions following SRS. The growth pattern of 22 unirradiated lesions during an observation period of 83.4 (61.1-120.4) months was separately evaluated.ResultsMost treated lesions showed effective tumor control up to 85% at 60 months after SRS, whereas unirradiated lesions progressed with a relative volume increase of 14.0% (7.8-27.0) per year during the observation period. Twelve (29%) cases showed pseudoprogression with significant volume expansion in the early follow-up period, which practically reduced the rate of tumor control to 57% at 24 months. Among the patients with serviceable hearing, two (20%) cases lost the hearing function on the treated side during the early follow-up period within 24 months.ConclusionsProgressive NF2-associated VS can be adequately controlled by SRS but the short-term effects of this treatment are not highly advantageous in terms of preserving hearing function. SRS treatment candidates should therefore be carefully selected.

Although the importance of proper pharmacological treatment for preventing the relapse/recurrence of anxiety disorders is well known, a real-world data-based study has not been conducted. We aimed to investigate the effect of the initial pharmacological patterns related to continuous treatment and the choice of medication on the relapse/recurrence of anxiety disorders. We used claim data from the Health Insurance Review and Assessment Service, South Korea, of 34,378 adults who received psychiatric medications, including antidepressants, after being newly diagnosed with anxiety disorders. We compared the relapse/recurrence rate in the patients receiving continuous pharmacological treatment with those who discontinued treatment early using Cox’s proportional-hazards model. Patients receiving continuous pharmacological treatment experienced a higher risk of relapse/recurrence than those who discontinued treatment. Using three or more antidepressants during the initial treatment period decreased the risk of relapse/recurrence (adjusted hazard ratio (aHR) = 0.229 (0.204–0.256)); however, the combined use of antidepressants from the beginning of treatment increased the risk (aHR = 1.215 (1.131–1.305)). Factors other than continuous pharmacological treatment should be considered to effectively prevent the relapse/recurrence of anxiety disorders. The active use of antidepressants, including switching or adding medications based on progress and frequent follow-up visits during the acute phase, were significantly associated with a reduction in the relapse/recurrence of anxiety disorders.

BackgroundGrade 2/3 meningiomas have locally aggressive behaviors often requiring additional treatment plans after surgical resection. Herein, we explored the clinical significance of next-generation sequencing (NGS) in characterizing the molecular profiles of high-grade meningiomas.MethodsPatients with intracranial meningioma who underwent surgical resection in a single institution were retrospectively reviewed. Clinicopathologic relevance was evaluated using recurrence-free survival (RFS) as an outcome measure. NGS for the targeted gene regions was performed in 40 participants.ResultsAmong the 713 individuals in the study population, 143 cases (20.1%) were identified as having grade 2 or 3 meningiomas with a significantly lower female predominance. While the difference in RFS between grade 2 and 3 meningiomas was insignificant, a few conventional grade 2 cases, but with TERT promoter hotspot mutation, were highly progressive and refractory to the treatment. From the NGS study, recurrent mutations in TRAF and AKT1 were identified with a higher prevalence (17.5% and 12.5%, respectively) compared with grade 2/3 meningiomas reported in previous literature. However, their relations to other histopathologic properties or clinical factors were rarely observed.ConclusionsGrade 2/3 meningiomas show a broad spectrum of molecular profiles, as they have heterogeneous histologic characteristics.

Recently, thanks to various support mechanisms, residential photovoltaics (PVs) for self-consumption are proliferating at a rapid pace. The net-metering scheme, one of the prevailing support mechanisms for self-consumption PVs, contributes to the proliferation of residential PVs by enhancing the economic benefits of PV adopters, but it suffers from certain disadvantages, such as missing network revenue of utilities and spread of cross-subsidies between the customers. This paper analyzes the cross-subsidy effect of residential PV proliferation across customer groups segmented according to their PV adoption and electricity consumption level under the net-metering scheme in the Korean electricity market. The results show that missing network revenue of utilities increase by about 0.83% for every 1% increase of residential PV penetration, and customers in the lowest usage tier provide more cross-subsidies toward customers in the higher usage tiers as with higher proliferation of residential PVs. In addition, this paper suggests that the cross-subsidy effect between customers can be reduced by introducing a new network charge design that is more consistent with the cost-causality principle as well as targeted deployment policies for self-consumption PVs.

SLC6A20A is a proline and glycine transporter known to regulate glycine homeostasis and NMDA receptor (NMDAR) function in the brain. A previous study found increases in ambient glycine levels and NMDA receptor-mediated synaptic transmission in the brains of Slc6a20a-haploinsufficient mice, but it remained unknown whether Slc6a20a deficiency leads to disease-related behavioral deficits in mice. Here, we report that Slc6a20a heterozygous and homozygous mutant mice display differential behavioral phenotypes in locomotor, repetitive behavioral, and spatial and fear memory domains. In addition, these mice show differential transcriptomic changes in synapse, ribosome, mitochondria, autism, epilepsy, and neuron-related genes. These results suggest that heterozygous and homozygous Slc6a20a deletions in mice lead to differential changes in behaviors and transcriptomes.

Most studies have classified older adults with diabetes into one group despite substantial variation in health status across different stages of late adulthood. In this study, we examined difference in self-reported physical and mental health among three age groups of older adults with diabetes. Using data from the 2016 National Social Life, Health and Aging Project, Wave 3, we classified 424 individuals diagnosed with diabetes into three age groups, young-old (YO): 50–64 years; middle-old (MO): 65–74; and oldest old (OO): 75+ years. A one-way multivariate analysis of covariance was used to assess group differences, followed by univariate analyses. The results indicate that the YO group reported significantly lower physical health and higher depression than the MO group and higher levels of loneliness than the MO and OO groups. These findings indicate that physical and mental health may differ among different age groups of older adults with diabetes and suggest that the YO might be more vulnerable to diminished physical and mental health than the other age groups.

Epidermoid cysts are commonly encountered benign lesions in the field of plastic surgery, but their malignant transformation into squamous cell carcinoma (SCC) is extremely rare. A 68-year old woman with a cystic mass on her left lower back presented to our department. We excised the lesion under the suspicion of an epidermoid cyst or metastatic colon cancer based on the patient’s medical history. The skin defect was covered with a split-thickness skin graft, and histopathological evaluation revealed the presence of SCC. Because of the low incidence of SCC arising from an epidermoid cyst, the mechanism of transformation of such cysts to SCC and the prognosis of this condition have not yet been well established. We therefore share the details of this rare case to contribute to the growing base of knowledge about SCC that arises from an epidermoid cyst.

Abstract Background Functional communication is vital in many areas of daily life, and modifying dysfunctional communication has been emphasized in various social areas, including family and school. The present preliminary study addressed the feasibility of a virtual reality (VR)-based interactive feedback program for the modification of dysfunctional communication. Methods Thirty-seven healthy young males completed psychological assessments associated with functional communication and participated in the VR-based program, consisting of the three tasks of ‘exploring the communication style,’ ‘practicing functional communication,’ and ‘expressing empathy.’ Behavioral parameters were recorded based on the participants’ choices among available options and the visual analog scale scores that resulted in responses to questions in the tasks. Results Participants completed the program without dropping-out and reported 10.76 (SD, 9.66) in the Simulator Sickness Questionnaire and 106.97 (SD, 16.66) in the Presence Questionnaire. In exploring the communication style, there was no difference between the dysfunction level-with family and dysfunction level-with a friend, but only the dysfunction level-with family showed significant correlations with the level of communication with parents. In practicing functional communication, the communication scores with the placating, blaming, and computing styles significantly increased according to the repetition of trials. In expressing empathy, the empathetic feeling score was negatively correlated with the perspective-taking score, whereas the emotional intensity score was positively correlated with the level of differentiation of the self. Conclusion These results suggest that the program may have a tolerable level of cybersickness, an adequate level of presence, an improvement in the behavioral parameters that may reflect the important aspects of communication, and a proper reflection of psychological states or interpersonal characteristics. The use of this program can be an important starting point for the development of a more convenient method for delivering VR programs designed to modify dysfunctional communication, which can further increase computerized dissemination.

Background: We assessed the anthropometric measurements of bone defects in microform cleft lip. Methods: The external phenotypes of the nose and upper lip, and alveolar bone defects in microform cleft lip were measured anthropometrically using multimodal tools and clinical photographs. The height and thickness of the alveolar bone, paranasal hypoplasia, and alveolar volume were measured on CT. Results: Our study included 23 patients with unilateral microform cleft lip. The mean age of the patients was 13.84 ± 12.35 years (range: 1.25–50 years). Alveolar height (C1), thickness (C2), and paranasal hypoplasia (C3) were evaluated on 3D CT scans. The mean differences in C1, C2, and C3 between the cleft and normal sides were 5.52 ± 3.76 mm (p < 0.0001), 1.96 ± 2.8 mm (p < 0.0001), and 5.57 ± 9.72 mm (p < 0.0001), respectively. There was bony deficiency at the cleft side of the alveolar bone and paranasal area. In volumetric analysis, the means of the normal and cleft-side alveolar bone volumes were 6579 ± 2200 mm3 and 6528 ± 2255 mm3, respectively. The mean difference in alveolar bone volume between the cleft and normal sides was 51.05 ± 521 mm3 (p < 0.0001). C1 was positively correlated with lip height (F2; correlation coefficient (r) = 0.564, p = 0.0051) and dry vermilion thickness (F3; r = −0.543, p = 0.0074). The linear regression test revealed significant correlations between C1 and F2 (r2 = 0.318, p = 0.0051), and F3 (r2 = 0.295, p = 0.0074). However, there was no correlation between alveolar height and nasal anthropometric measurements. Conclusions: Alveolar bone deficiency was concordant with the severity of soft tissue in microform cleft lip.

Global automakers are speeding up both the suspension of production of internal combustion engine vehicles and the transition to electric vehicles (EVs) in order to respond to global goals to become carbon-free and energy-efficient. Recently, vehicle-to-grid (V2G) technology has reached the commercialization stage in Korea. Many studies have mostly discussed profits that an EV owner can make by participating in a regulation program. However, all the stakeholders who are involved with V2G service have not been sufficiently considered. Thus, we propose a novel framework for the economic valuation of V2G in ancillary service. Furthermore, to estimate the available capacity of V2G and find an optimal strategy in order for the V2G service to run, a data-driven approach is proposed in this research. Comprehensive simulation results show the optimal situation requiring the minimum financial support for the EV owner when the V2G-service operator aggregates AC chargers. In addition, promotions from government and public utilities can accelerate the V2G service into the ancillary service. As a final remark, given the flexibility of the proposed framework, it could be adapted to validate its performance in other countries, as part of future works.

Background: We analyzed an original case series of the classic ear-molding method and evaluated the efficacy and complication rate of the method compared to commercial ear-molding products by meta-analysis to draw conclusions on the efficacy of the classic method. Methods: From January 2019 to March 2022, we selected patients who underwent classic ear molding for newborn ear deformities at our institution and reviewed the patient age, treatment time, efficiency and complications. Additionally, the PubMed, EMBASE, and Scopus databases were searched, and meta-analysis (following the PRISMA guidelines) was performed. Results: In the case study, the success rate (excellent and good outcomes) of the classic ear-molding method was 92.6%. The mean age at application and mean duration of application were 5.81 ± 6.09 days and 32.13 ± 7.90 days, respectively. In the systematic review, the classic method group showed a statistically smaller success rate (proportion of 0.79) and statistically smaller complication rate (proportion of 0.05) than the commercial product group (proportion of 0.83). Conclusions: Compared with commercial products, classic ear molding has remarkable and comparable therapeutic effects on neonatal auricular deformities. Additionally, the classic ear-molding method is more suitable for infants with auricular deformities from socioeconomically vulnerable areas. Thus, the classic ear-molding method could be a better option for congenital ear anomalies than commercial ear-molding products.

Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Mitochondrial dysfunction is linked to oxidative stress and reactive oxygen species (ROS) in neurotoxicity during AD. Impaired mitochondrial metabolism has been associated with mitochondrial dysfunction in brain damage of AD. While the role of NADPH oxidase 4 (NOX4), a major source of ROS, has been identified in brain damage, the mechanism by which NOX4 regulates ferroptosis of astrocytes in AD remains unclear. Here, we show that the protein levels of NOX4 were significantly elevated in impaired astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD. The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD. We demonstrate that the over-expression of NOX4 significantly increases the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production via the reduction of five protein complexes in the mitochondrial ETC in human astrocytes. Moreover, the elevation of NOX4 induces oxidative stress by mitochondrial ROS (mtROS) production, mitochondrial fragmentation, and inhibition of cellular antioxidant process in human astrocytes. Furthermore, the elevation of NOX4 increased ferroptosis-dependent cytotoxicity by the activation of oxidative stress-induced lipid peroxidation in human astrocytes. These results suggest that NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in AD.

Abstract Background Originating from poultry, particularly chickens, Campylobacter jejuni is the leading foodborne pathogen worldwide and a major cause of campylobacteriosis. Isolating C. jejuni is difficult due to its specific growth requirements, the presence of viable but non-culturable bacteria, and because it is often masked by competing flora. Currently, there is no optimized method for isolating C. jejuni from chicken feces. Here, we evaluated the method for isolating C. jejuni from chicken feces using culture-independent sequence-based metagenomics and culture-dependent tools. Further, we assessed changes in microbial communities during microbe isolation to determine how the process can be improved. Results Fourteen different variations of C. jejuni isolation procedures were applied to all 35 chicken fecal samples. These variations included using different enrichment broths (without enrichment or enrichment in Bolton or Preston broth), different ratios of sample-to-enrichment broth (1:101, 1:102, and 1:103), and different selective agars (modified charcoal-cefoperazone-deoxycholate agar (mCCDA) or Preston agar). Enrichment during isolation of C. jejuni was evaluated on the basis of microbial diversity and taxonomic composition using metagenomics tools. The effect of selective media was evaluated using a combination of metagenomics and culture-dependent tools. Microbial diversity significantly decreased during the enrichment process, regardless of the type of enrichment broth, with the most significant decrease observed at a feces-to-broth ratio of 1:103. Particularly, in 103-Preston broth, the relative abundance of Campylobacter increased, while extended-spectrum beta-lactamase-producing Escherichia coli, which interfere with Campylobacter isolation, decreased. Metagenomics results were validated by quantitative PCR and culture-dependent analysis. Additionally, selective media affected the isolation results, although microbes with high relative abundance during enrichment were also frequently isolated using culture-dependent methods. Significantly more C. jejuni was isolated from mCCDA than from Preston agar enriched in 103 Preston broth. Conclusions Enrichment in Preston broth at a ratio of 1:103 followed by spreading onto mCCDA was the most effective method for isolating C. jejuni. This is the first study to apply metagenomics to evaluate a method for isolating a targeted microbe, C. jejuni, from chicken feces, a source with high microbial contamination. Thus, metagenomics can be applied to improve methods for isolating bacteria that are difficult to separate.

Campylobacter, the most common etiologic agent of zoonotic gastroenteritis in humans, is present in many reservoirs including livestock animals, wildlife, soil, and water. Previously, we reported a novel Campylobacter jejuni strain SCJK02 (MLST ST-8388) from the gut of wild mice (Micromys minutus) using culture-dependent methods. However, due to fastidious growth conditions and the presence of viable but non-culturable Campylobacter spp., it is unclear whether M. minutus is a Campylobacter reservoir. This study aimed to: 1) determine the distribution and proportion of Campylobacter spp. in the gut microbiota of wild mice using culture-independent methods and 2) investigate the gut microbiota of wild mice and the relationship of Campylobacter spp. with other gut microbes. The gut microbiota of 38 wild mice captured from perilla fields in Korea and without any clinical symptoms (18 M. minutus and 20 Mus musculus) were analyzed. Metagenomic analysis showed that 77.8% (14 of 18) of the captured M. minutus harbored Campylobacter spp. (0.24–32.92%) in the gut metagenome, whereas none of the captured M. musculus carried Campylobacter spp. in their guts. Notably, 75% (6 of 8) of M. minutus determined to be Campylobacter-negative using culture-dependent methods showed a high proportion of Campylobacter through metagenome analysis. The results of metagenome analysis and the absence of clinical symptoms suggest that Campylobacter may be a component of the normal gut flora of wild M. minutus. Furthermore, linear discriminant analysis (LDA) showed that Campylobacter was the most enriched genus in the gut microbiota of M. minutus (LDA score, 5.37), whereas Lactobacillus was the most enriched genus in M. musculus (LDA score, −5.96). The differences in the presence of Campylobacter between the two species of wild mice may be attributed to the differential abundance of Campylobacter and Lactobacillus in their respective gut microbiota. In conclusion, the results indicate that wild M. minutus may serve as a potential Campylobacter reservoir. This study presents the first metagenomics analysis of the M. minutus gut microbiota to explore its possible role as an environmental Campylobacter reservoir and provides a basis for future studies using culture-independent methods to determine the role of environmental reservoirs in Campylobacter transmission.

Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.

High aggression is common and costly for mental health problems in young adults. Because communication is a universal part of social relationships, including conflicts with others, it could be a possible target for mediating aggression. This study aimed to evaluate whether the virtual reality (VR)-based communication modification program can be utilized for aggression management. Fifty-eight individuals with high aggression (n = 30) and with low aggression (n = 28) completed psychological assessments associated with aggression and functional communication, and they participated in the program, consisting of the three tasks: exploring the communication style, practicing functional communication, and expressing empathy. The participants’ selections and their visual analog scale scores, in response to questions in the tasks, were collected as behavioral data. Results indicated that the high aggression group selected blaming dysfunctional communication style more frequently than the low aggression group. VR-based parameters, expected to reflect dysfunctional communication-related characteristics, showed significantly different correlations with aggression-related traits between the two groups. These findings show that our program may accurately represent an individual’s aggressive traits and elicit the appropriate reaction.

The alteration of the cellular metabolism is a hallmark of glioma. The high glycolytic phenotype is a critical factor in the pathogenesis of high-grade glioma, including glioblastoma multiforme (GBM). GBM has been stratified into three subtypes as the proneural, mesenchymal, and classical subtypes. High glycolytic activity was found in mesenchymal GBM relative to proneural GBM. NADPH oxidase 2 (NOX2) has been linked to cellular metabolism and epithelial-mesenchymal transition (EMT) in tumors. The role of NOX2 in the regulation of the high glycolytic phenotype and the gain of the mesenchymal subtype in glioma remain unclear. Here, our results show that the levels of NOX2 were elevated in patients with GBM. NOX2 induces hexokinase 2 (HK2)-dependent high glycolytic activity in U87MG glioma cells. High levels of NOX2 are correlated with high levels of HK2 and glucose uptake in patients with GBM relative to benign glioma. Moreover, NOX2 increases the expression of mesenchymal-subtype-related genes, including COL5A1 and FN1 in U87MG glioma cells. High levels of NOX2 are correlated with high levels of COL5A1 and the accumulation of extracellular matrix (ECM) in patients with GBM relative to benign glioma. Furthermore, high levels of HK2 are correlated with high levels of COL5A1 in patients with GBM relative to benign glioma. Our results suggest that NOX2-induced high glycolytic activity contributes to the gain of the COL5A1-mediated mesenchymal phenotype in GBM.

Purpose: Fillet flap is a “spare part” concept. This technique allows the defect to be covered without donor site morbidity. Over the past 5 years, there were 107 diabetic foot cases of one-toe fillet flap in our hospital. After the operation, in some patients, there was necrosis of the adjacent toe that required additional amputation. The aim of our study was to determine the cause of necrosis of the adjacent toe after fillet flap. Methods: The patients were divided into two groups. One group had no necrosis of the adjacent toe (group A) after the operation, and the other group had necrosis of the adjacent toe that required additional amputation after the operation (group B). Then, to confirm the cause of the additional necrosis of the adjacent toe, χ 2 tests, Fisher’s tests, and logistic regression tests were performed. Results: A total of 107 patients were included, and 48 patients needed additional amputation. The logistic regression test revealed that a fillet flap at the metatarsophalangeal joint (MTPJ), horizontal sutures, and a fillet flap at the second toe were significant risk factors for developing necrosis. Conclusions: If a fillet flap with a second toe, fillet flap on MTPJ level and horizontal closure after fillet flap is needed, the chance of developing necrosis of the adjacent toe and additional revisional surgery must be communicated preoperatively.

Self-respect is a practical way to promote life satisfaction through gratifying basic psychological needs, whereas self-criticism is associated with life dissatisfaction. The goal of the present study was to investigate the effect of two positive and negative self-talks on the functional connectome with respect to life satisfaction and its relationships with basic psychological needs. Forty-eight individuals with low life satisfaction (LLS, n ​= ​24) and with high life satisfaction (HLS, n ​= ​24) were scanned using functional magnetic resonance imaging at a baseline state and during and after self-respect or self-criticism tasks. Functional connectivity analysis was conducted to identify the modulatory effects of the tasks on the self-referential, default mode, and reward-motivation networks. We found that self-respect changed only the connection between the posterior cingulate cortex (PCC) and frontoparietal network, whereas self-criticism changed almost all of the connections examined. The group x condition interaction effect of self-respect was identified only in connection between the PCC and left ventrolateral prefrontal cortex, while that of self-criticism was observed in various connections based on the ventromedial prefrontal cortex and nucleus accumbens. In respect to basic psychological needs, functional connectivity after self-criticism was significant in predicting the needs of autonomy and relatedness only in the LLS group, whereas functional connectivity after self-respect could predict the needs of autonomy and competence only in the HLS group. Overall, self-criticism produces more noticeable negative changes in the brain than the positive changes of self-respect. Individuals with low life satisfaction may be more vulnerable to be negatively affected not only by self-criticism but also self-respect than individuals with high life satisfaction. The satisfaction of basic psychological needs can play a mediating role in the effects of self-talk tasks differently concerning life satisfaction.

Campylobacter jejuni is one of the most common zoonotic pathogens worldwide. Although the main sources of human C. jejuni infection are livestock, wildlife can also affect C. jejuni transmission in humans. However, it remains unclear whether wild mice harbor C. jejuni and are involved in the “environment–wildlife–livestock–human” transmission cycle of C. jejuni in humans. Here, we characterized C. jejuni from wild mice and identified genetic traces of wild mouse-derived C. jejuni in other hosts using a traditional approach, along with comparative genomics. We captured 115 wild mice (49 Mus musculus and 66 Micromys minutus) without any clinical symptoms from 22 sesame fields in Korea over 2 years. Among them, M. minutus were typically caught in remote areas of human houses and C. jejuni was solely isolated from M. minutus (42/66, 63.6%). We identified a single clone (MLST ST-8388) in all 42 C. jejuni isolates, which had not been previously reported, and all isolates had the same virulence/survival-factor profile, except for the plasmid-mediated virB11 gene. No isolates exhibited antibiotic resistance, either in phenotypic and genetic terms. Comparative-genomic analysis and MST revealed that C. jejuni derived from M. minutus (strain SCJK2) was not genetically related to those derived from other sources (registered in the NCBI genome database and PubMLST database). Therefore, we hypothesize that C. jejuni from M. minutus is a normal component of the gut flora following adaptation to the gastro-intestinal tract. Furthermore, M. minutus-derived C. jejuni had different ancestral lineages from those derived from other sources, and there was a low chance of C. jejuni transmission from M. minutus to humans/livestock because of their habitat. In conclusion, M. minutus may be a potential reservoir for a novel C. jejuni, which is genetically different from those of other sources, but may not be involved in the transmission of C. jejuni to other hosts, including humans and livestock. This study could form the basis for further studies focused on understanding the transmission cycle of C. jejuni, as well as other zoonotic pathogens originating from wild mice.

We performed an animal study to identify the techniques associated with the best muscle healing outcomes in cleft lip/palate surgery. The right triceps of thirty adult male Sprague–Dawley rats were cut and repaired by three different suture techniques: simple (n = 10), overlapping (n = 10), and splitting sutures (n = 10). Muscle tissues were isolated from 5 rats per group 1 and 8 weeks postoperation. The inflammatory response and muscle fiber healing were evaluated by hematoxylin and eosin (H&E) staining, Western blotting, immunohistochemistry for TNF-α and IL-1β, and immunofluorescence for laminin and MyoD. Grip strength (N/100 g) and spatial gait symmetry were evaluated before surgery and 1, 2, 4 and 8 weeks postoperation. Eight weeks postoperation, grip force per weight was significantly higher in the simple suture (median, 3.49; IQR, 3.28–3.66) and overlapping groups (median, 3.3; IQR, 3.17–3.47) than the splitting group (median, 2.91; IQR, 2.76–3.05). There was no significant difference in range of motion between groups. The simple group exhibited significant remission of inflammation by H&E staining and lower expression of TNF-α and IL-1β than the other groups by Western blotting and immunohistochemistry. Immunofluorescence revealed stronger expression of MyoD and weaker expression of laminin in the splitting group than in the other groups at week 8, indicating prolonged inflammation and healing followed by poor muscle fiber remodeling. Simple and overlapping sutures demonstrated similar functional healing, although greater inflammation and failure to maintain a thicker muscle belly were observed in the overlapping suture group compared with the simple suture group. Therefore, reconstruction of the philtral column with overlapping sutures alone may result in limited long-term fullness, and additional procedures may be needed.

Abstract Background Recent advances in next-generation sequencing technologies have enabled comprehensive analysis of the gut microbiota, which is closely linked to the health of the host. Consequently, several studies have explored the factors affecting gut microbiota composition. In recent years, increasing number of dog owners are feeding their pets a natural diet i.e., one consisting of bones, raw meat (such as chicken and beef), and vegetables, instead of commercial feed. However, the effect of these diets on the microbiota of dogs (Canis lupus familiaris) is unclear. Methods and results Six dogs fed a natural diet and five dogs fed a commercial feed were selected; dog fecal metagenomic DNA samples were analyzed using the Illumina MiSeq platform. Pronounced differences in alpha and beta diversities, and taxonomic composition of the core gut microbiota were observed between the two groups. According to alpha diversity, the number of operational taxonomic units, the richness estimates, and diversity indices of microbiota were significantly higher (p

Background Polydeoxyribonucleotide (PDRN) is known to have anti-inflammatory and angiogenic effects and to accelerate wound healing. The aim of this study was to investigate whether PDRN could improve peripheral tissue oxygenation and angiogenesis in diabetic foot ulcers. Methods This was a prospective randomized controlled clinical trial. Twenty patients with a non-healing diabetic foot ulcer were randomly distributed into a control group (n=10) and a PDRN group (n=10). Initial surgical debridement and secondary surgical procedures such as a split-thickness skin graft, primary closure, or local flap were performed. Between the initial surgical debridement and secondary surgical procedures, 0.9% normal saline (3 mL) or PDRN was injected for 2 weeks by the intramuscular (1 ampule, 3 mL, 5.625 mg, 5 days per week) and perilesional routes (1 ampule, 3 mL, 5.625 mg, 2 days per week). Transcutaneous oxygen tension (TcPO2) was evaluated using the Periflux System 5000 with TcPO2/CO2 unit 5040 before the injections and on days 1, 3, 7, 14, and 28 after the start of the injections. A pathologic review (hematoxylin and eosin stain) of the debrided specimens was conducted by a pathologist, and vessel density (average number of vessels per visual field) was calculated. Results Compared with the control group, the PDRN-treated group showed improvements in peripheral tissue oxygenation on day 7 (P

Bone morphogenetic protein-2 (BMP-2) is widely used to enhance bone regeneration. However, because of its short half-life and rapid disappearance, large amounts of BMP-2 are needed, leading to unintended side effects. In this study, BMP-2-encapsulated alginate microbeads (AM) were used to enhance bone regeneration. Enzyme-linked immunosorbent assay confirmed the sustained release of BMP-2 from AM. Vascular endothelial growth factor (VEGF)-adsorbing aptamer-conjugated hydroxyapatite (Apt-HA) was used for osteoconduction and dual delivery of VEGF and BMP-2. For in vivo bone regeneration evaluation, the grafts (1) Apt-HA + phosphate-buffered saline (PBS), (2) Apt-HA + AM without BMP-2, (3) Apt-HA + BMP-2, and (4) Apt-HA + AM encapsulated with BMP-2 were implanted into rabbit tibial metaphyseal defects. After four weeks, micro-computed tomography (CT), histological, and histomorphometric analyses were performed to evaluate bone regeneration. The Apt-HA + AM with BMP-2 group revealed a significantly higher new bone volume and bone volume/total volume (BV/TV) in both cortical and trabecular bone than the others. Furthermore, as evaluated by histomorphometric analysis, BMP-2 AM exhibited a significantly higher bone formation area than the others, indicating that AM could be used to efficiently deliver BMP-2 through sustained release. Moreover, the combined application of BMP-2-encapsulated Apt-HA + AM may effectively promote bone regeneration.

(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.

Abstract Background As a primary source of Shiga-toxin-producing Escherichia coli (STEC) infection, cattle are often targeted to develop strategies for reducing STEC contamination. Monitoring the virulence potentials of STEC isolates from cattle is important for tracing contamination sources, managing outbreaks or sporadic cases, and reducing the risks for human infection. This study aimed to investigate the prevalence of STEC in cattle farm samples in South Korea and to assess their virulence potentials. Results In total, 63 STEC were isolated from 496 cattle farm samples, and temperature and rainfall affected STEC prevalence (p

Since contaminated poultry meat is the major source of transmitting Campylobacter jejuni to humans, the isolation of Campylobacter from poultry carcasses is frequently performed in many countries as a baseline survey to ensure food safety. However, existing isolation methods have technical limitations in isolating this fastidious bacterium, such as a growth competition with indigenous bacteria in food samples. In this study, we compared the differences in microbiota compositions between Bolton and Preston selective media, two most common selective media to isolate Campylobacter, and investigated how different microbiota compositions resulting from different enrichment methods may affect isolation frequencies. A next-generation sequencing (NGS) analysis of 16S rRNA demonstrated that Bolton and Preston-selective enrichments generated different microbiota structures that shared only 31.57% of Operating Taxonomic Unit (OTU) types. Particularly, Escherichia was highly prevalent in Bolton selective media, and the enrichment cultures that increase Escherichia negatively affected the efficacy of Campylobacter isolation. Furthermore, the combination of the selective media made a significant difference in the isolation frequency. The Bolton broth and Preston agar combination exhibited the highest (60.0%) frequencies of Campylobacter isolation, whereas the Bolton broth and Bolton agar combination showed the lowest (2.5%). These results show that each selective medium generates a unique microbiota structure and that the sequence of combining the selective media also critically affects the isolation frequency by altering microbiota compositions. In this study, we demonstrated how a microbiota analysis using NGS can be utilized to optimize a protocol for bacterial isolation from food samples.

Protein thermal stability is an important field since thermally stable proteins are desirable in many academic and industrial settings. Information on protein thermal stabilization can be obtained by comparing homologous proteins from organisms living at distinct temperatures. Here, we report structural and mutational analyses of adenylate kinases (AKs) from psychrophilic Bacillus globisporus (AKp) and mesophilic Bacillus subtilis (AKm). Sequence and structural comparison showed suboptimal hydrophobic packing around Thr26 in the CORE domain of AKp, which was replaced with an Ile residue in AKm. Mutations that improved hydrophobicity of the Thr residue increased the thermal stability of the psychrophilic AKp, and the largest stabilization was observed for a Thr-to-Ile substitution. Furthermore, a reverse Ile-to-Thr mutation in the mesophilic AKm significantly decreased thermal stability. We determined the crystal structures of mutant AKs to confirm the impact of the residue substitutions on the overall stability. Taken together, our results provide a structural basis for the stability difference between psychrophilic and mesophilic AK homologues and highlight the role of hydrophobic interactions in protein thermal stability.

Campylobacter jejuni is a major foodborne pathogen that is increasingly found worldwide and that is transmitted to humans through meat or dairy products. A detailed understanding of the prevalence and characteristics of C. jejuni in dairy cattle farms, which are likely to become sources of contamination, is imperative and is currently lacking. In this study, a total of 295 dairy cattle farm samples from 15 farms (24 visits) in Korea were collected. C. jejuni prevalence at the farm level was 60% (9/15) and at the animal level was 23.8% (68/266). Using the multivariable generalized estimating equation (GEE) model based on farm-environmental factors, we estimated that a high density of cattle and average environmental temperature (7 days prior to sampling) below 24°C affects the presence and survival of C. jejuni in the farm environment. Cattle isolates, together with C. jejuni from other sources (chicken and human), were genetically characterized based on analysis of 10 virulence and survival genes. A total of 19 virulence profile types were identified, with type 01 carrying eight genes (all except hcp and virB11) being the most prevalent. The prevalence of virB11 and hcp was significantly higher in isolates from cattle than in those from other sources (p < 0.05). Multilocus sequence typing (MLST) of C. jejuni isolates from three different sources mainly clustered in the CC-21 and CC-48. Within the CC-21 and CC-48 clusters, cattle isolates shared an indistinguishable pattern with human isolates according to pulsed-field gel electrophoresis (PFGE) and flaA-restriction fragment length polymorphism (RFLP) typing. This suggests that CC-21 and CC-48 C. jejuni from dairy cattle are genetically related to clinical campylobacteriosis isolates. In conclusion, the farm environment influences the presence and survival of C. jejuni, which may play an important role in cycles of cattle re-infection, and dairy cattle represent potential reservoirs of human campylobacteriosis. Thus, environmental management practices could be implemented on cattle farms to reduce the shedding of C. jejuni from cattle, subsequently reducing the potential risk of the spread of cattle-derived C. jejuni to humans through the food chain.

Alzheimer’s disease (AD) is the most common type of dementia, and depression is a risk factor for developing AD. Epidemiological studies provide a clinical correlation between late-life depression (LLD) and AD. Depression patients generally remit with no residual symptoms, but LLD patients demonstrate residual cognitive impairment. Due to the lack of effective treatments, understanding how risk factors affect the course of AD is essential to manage AD. Advances in neuroimaging, including resting-state functional MRI (fMRI), have been used to address neural systems that contribute to clinical symptoms and functional changes across various psychiatric disorders. Resting-state fMRI studies have contributed to understanding each of the two diseases, but the link between LLD and AD has not been fully elucidated. This review focuses on three crucial and well-established networks in AD and LLD and discusses the impacts on cognitive decline, clinical symptoms, and prognosis. Three networks are the (1) default mode network, (2) executive control network, and (3) salience network. The multiple properties emphasized here, relevant for the hypothesis of the linkage between LLD and AD, will be further developed by ongoing future studies.

Background Facial hypoesthesia is one of the most troublesome complaints in the management of facial bone fractures. However, there is a lack of literature on facial sensory recovery after facial trauma. The purpose of this study was to evaluate the facial sensory recovery period for facial bone fractures using Neurometer. Methods Sixty-three patients who underwent open reduction of zygomatic and blowout fractures between December 2013 and July 2015 were included in the study. The facial sensory status of the patients was repeatedly examined preoperatively and postoperatively by Neurometer current perception threshold (CPT) until the results were normalized. Results Among the 63 subjects, 30 patients had normal Neurometer results preoperatively and postoperatively. According to fracture types, 17 patients with blowout fracture had a median recovery period of 0.25 months. Twelve patients with zygomatic fracture had a median recovery period of 1.00 month. Four patients with both fracture types had a median recovery period of 0.625 months. The median recovery period of all 33 patients was 0.25 months. There was no statistically significant difference in the sensory recovery period between types and subgroups of zygomatic and blowout fractures. In addition, there was no statistically significant difference in the sensory recovery period according to Neurometer results and the patients' own subjective reports. Conclusions Neurometer CPT is effective for evaluating and comparing preoperative and postoperative facial sensory status and evaluating the sensory recovery period in facial bone fracture patients.

It is demonstrated that the heart-rate can be sensed capacitively on a touch screen panel (TSP) together with touch signals. The existing heart-rate sensing systems measure blood pulses by tracing the amount of light reflected from blood vessels during a number of cardiac cycles. This type of sensing system requires a considerable amount of power and space to be implemented in multi-functional mobile devices such as smart phones. It is found that the variation of the effective dielectric constant of finger stemming from the difference of systolic and diastolic blood flows can be measured with laterally interspaced top electrodes of TSP. The spacing between a pair of non-adjacent top electrodes turns out to be wide enough to distinguish heart-rate signals from noises. With the aid of fast Fourier transform, the heart-rate can be extracted reliably, which matches with the one obtained by actually counting heart beats on the wrist.

A stretchable printed circuit board (PCB), which is an essential component of next-generation electronic devices, should be highly stretchable even at high levels of integration, as well as durable under repetitive stretching and patternable. Herein, an island-structured stretchable PCB composed of materials with controlled Young’s modulus and viscosity by adding a reinforcing agent or controlling the degree of crosslinking is reported. Each material was fabricated with the most effective structures through a 3D printer. The PCB was able to stretch 71.3% even when highly integrated and was patterned so that various components could be mounted. When fully integrated, the stress applied to the mounted components was reduced by 99.9% even when stretched by over 70%. Consequently, a 4 × 4 array of capacitance sensors in a stretchable keypad demonstration using our PCB was shown to work, even at 50% stretching of the PCB.