Characterization of the Outer Membrane Vesicles of Pseudomonas aeruginosa Exhibiting Growth Inhibition against Acinetobacter baumannii.

We investigated the Pseudomonas aeruginosa (PA) outer membrane vesicles (OMVs) and their effect on Acinetobacter baumannii (AB) growth in vitro. The inhibitory effects of PA on AB were assessed using a cross-streak assay. The OMVs were extracted through high-speed centrifugation, tangential flow filtration, and ultracentrifugation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs). Proteomic analysis was conducted to compare the OMVs of different PA strains. PA022 exhibited more pronounced inhibition of AB growth compared with PA ATCC 27853. TEM confirmed the presence of OMVs in both PA022 and PA ATCC 27853, revealing phospholipid bilayer structures. The NTA revealed similar sizes and concentrations. Proteomic analysis identified 623 and 538 proteins in PA022 and PA ATCC 27853 OMVs, respectively, with significant proportions of the outer membrane and extracellular proteins, respectively. Importantly, PA022 OMVs contained six known virulence factors and motility-associated proteins. This study revealed the unique characteristics of PA OMVs and their inhibitory effects on AB growth, shedding light on their role in bacterial interactions. Proteomic analysis provides valuable insights into potential pathogenic functions and therapeutic applications against bacterial infections.

Chemoembolization as first-line treatment for hepatocellular carcinoma invading segmental portal vein with tumour burden limited to a monosegmental level.

OBJECTIVES: To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver. METHODS: A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated. RESULTS: After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P = .02; HR, 1.60), beyond the up-to-11 criteria (P = .002; HR, 2.26), Child-Pugh class B (P = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months. CONCLUSIONS: Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment. ADVANCES IN KNOWLEDGE: (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n=192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization.

Br doping-induced evolution of the electronic band structure in dimorphic and hexagonal SnSe2 thermoelectric materials.

SnSe2 with its layered structure is a promising thermoelectric material with intrinsically low lattice thermal conductivity. However, its poor electronic transport properties have motivated extensive doping studies. Br doping effectively improves the power factor and converts the dimorphic SnSe2 to a fully hexagonal structure. To understand the mechanisms underlying the power factor improvement of Br-doped SnSe2, the electronic band parameters of Br-doped dimorphic and hexagonal SnSe2 should be evaluated separately. Using the single parabolic band model, we estimate the intrinsic mobility and effective mass of the Br-doped dimorphic and hexagonal SnSe2. While Br doping significantly improves the mobility of dimorphic SnSe2 (with the dominant hexagonal phase), it results in a combination of band convergence and band flattening in fully hexagonal SnSe2. Br-doped dimorphic SnSe2 is predicted to exhibit higher thermoelectric performance (zT ∼0.23 at 300 K) than Br-doped fully hexagonal SnSe2 (zT ∼0.19 at 300 K). Characterisation of the other, currently unidentified, structural phases of dimorphic SnSe2 will enable us to tailor the thermoelectric properties of Br-doped SnSe2.

A Review on the Use of Gold Nanoparticles in Cancer Treatment.

According to a 2020 WHO study, cancer is responsible for one in every six fatalities. One in four patients die due to side effects and intolerance to chemotherapy, making it a leading cause of patient death. Compared to traditional tumor therapy, emerging treatment methods, including immunotherapy, gene therapy, photothermal therapy, and photodynamic therapy, have proven to be more effective. The aim of this review is to highlight the role of gold nanoparticles in advanced cancer treatment. A systematic and extensive literature review was conducted using the Web of Science, PubMed, EMBASE, Google Scholar, NCBI, and various websites. Highly relevant literature from 141 references was chosen for inclusion in this review. Recently, the synergistic benefits of nano therapy and cancer immunotherapy have been shown, which could allow earlier diagnosis, more focused cancer treatment, and improved disease control. Compared to other nanoparticles, the physical and optical characteristics of gold nanoparticles appear to have significantly greater effects on the target. It has a crucial role in acting as a drug carrier, biomarker, anti-angiogenesis agent, diagnostic agent, radiosensitizer, cancer immunotherapy, photodynamic therapy, and photothermal therapy. Gold nanoparticle-based cancer treatments can greatly reduce current drug and chemotherapy dosages.

The mineralocorticoid receptor and extra-synaptic NMDA receptor in the lateral habenula involve in the vulnerability to early life stress in the maternal separation model.

The lateral habenula (LHb) plays a pivotal role in regulating emotional responses during stress reactions, and its hyperactivity has been associated with depression. Recently it has been demonstrated that chronic early-life stress results in individual differences in stress vulnerability among rodents. However, how synaptic function in the LHb varies between susceptibility and resilience to early life stress remains elusive. In this study, we used a maternal separation model to assign animals with different stress vulnerabilities into groups and investigated the synaptic responses in the LHb. Our findings indicate that synaptic long-term depression (LTD) was impaired and extra-synaptic LTD was enhanced in the LHb of the susceptible group. To mimic the synaptic alteration in stress situations, when administered corticosterone, a stress hormone, the intervention appeared to impair synaptic LTD in the LHb of the control group, through the activation of mineralocorticoid receptors (MR). Indeed, there was an up-regulation of MR mRNA observed in the susceptible group. Following there was an up-regulation of both NR2A and NR2B subunits in the LHb. These results indicated that MR and extra-synaptic NMDA receptors in LHb are critically engaged in the susceptibilities to stress. Furthermore, our findings propose potential therapeutic targets for alleviating stress-related symptoms.

Risk of venous thromboembolism in Korean patients with rheumatoid arthritis treated with Janus kinase inhibitors: A nationwide population-based study.

OBJECTIVE: There was a safety concern about an increased risk of thromboembolic events in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). This study aimed to determine the risk of venous thromboembolism (VTE) in Korean patients with RA treated with JAKis compared with tumour necrosis factor (TNF) inhibitors. METHODS: Using the National Health Insurance Service database between 2015 and 2019, patients with prevalent RA who started JAKi or TNF inhibitor were selected as the study population. All participants were naïve to targeted therapy. Patients that had experienced any VTE event or used anticoagulant agents within 30 days were excluded. Demographic and clinical characteristics were all balanced by stabilised inverse probability of treatment weighting (sIPTW) using propensity score. The Cox proportional hazard model considering death as a competing risk was used to evaluate the risk of VTE in JAKi users compared with TNF inhibitor users. RESULTS: A total of 4,178 patients were included: 871 JAKi users and 3,307 TNF inhibitor users were followed up for 1,029.2 person-years (PYs) and 5,940.3 PYs, respectively. With a balanced sample after sIPTW, the incidence rates (IR) of VTE were 0.06 per 100 PYs (95% confidence interval [CI] 0.00-1.23) in JAKi users and 0.38 per 100 PYs (95% CI 0.25-0.58) in TNF inhibitor users. The hazard ratio was 0.18 (95% CI 0.01-3.47) after adjusting for unbalanced variables after performing sIPTW. CONCLUSION: There is no increased risk of VTE in RA patients treated with JAKis compared with TNF inhibitors in Korea.

Safety Profiles of mRNA COVID-19 Vaccines Using World Health Organization Global Scale Database (VigiBase): A Latent Class Analysis.

INTRODUCTION: Although messenger RNA (mRNA) vaccines have been developed and widely utilized to mitigate the coronavirus disease (COVID-19) pandemic, it is essential to describe the adverse events (AEs) following immunization. This study aimed to identify the patterns associated with serious AE reports after mRNA COVID-19 vaccination in the World Health Organization (WHO)'s global scale database (VigiBase). METHODS: This study performed a latent class analysis (LCA) of reports of serious AEs following mRNA COVID-19 vaccination from VigiBase between December 28, 2020 , and February 28, 2022 (N = 312878). The Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) terms were selected for LCA. The reporting characteristics in accordance with the cluster were described. We used a multinomial logistic regression model to estimate the association between potential factors and each cluster. RESULTS: Five clusters of AE reports were distinguished through LCA: infection AEs (cluster 1), cardiac AEs (cluster 2), respiratory/thrombotic AEs (cluster 3), systemic AEs (cluster 4), and nervous system AEs (cluster 5). Compared to cluster 4, cluster 2 had a higher proportion of males (OR 2.98; 95% confidence interval (CI) 2.87-3.09), and cluster 1 had a longer time to onset than other AEs (≥ 14 days) (OR 16.2; 95% CI 15.5-16.9). CONCLUSION: Using LCA, we found five clusters of serious AEs following mRNA COVID-19 vaccination. Each cluster was distinguished by potential factors such as age, gender, region, and time to onset. We suggest that monitoring should carefully consider the patterns of young males with cardiac AEs and elderly individuals with thrombosis after respiratory AEs. Our findings could contribute to enhancing understanding of safety profiles and establishing management strategies for serious AEs of special interest following mRNA COVID-19 vaccination.

Association between malignancy risk and Janus kinase inhibitors versus tumour necrosis factor inhibitors in Korean patients with rheumatoid arthritis: a nationwide population-based study.

OBJECTIVE: To determine the risk of malignancy in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis) compared with tumour necrosis factor inhibitors (TNFis). METHODS: A retrospective cohort of patients with RA initiating their first JAKi or TNFi was established using the Korean National Health Insurance database between 2015 and 2019. They were followed up from treatment initiation to the occurrence of malignancy, drug discontinuation, death or until December 2019. Baseline features of the patients were balanced through inverse probability of treatment weighting (IPTW) using a propensity score. A Cox proportional hazard model was established to estimate the HR for malignancy risk in JAKi users compared with TNFi users. RESULTS: A total of 4929 patients (1064 JAKi-treated and 3865 TNFi-treated patients) were included, and the observation periods were 1288.6 person-years (PYs) for JAKi users and 6823.8 PYs for TNFi users. The incidence rates of overall malignancy were 0.54 per 100 PYs (95% CI 0.26 to 1.14) in JAKi users and 0.85 per 100 PYs (95% CI 0.66 to 1.10) in TNFi users. In IPTW analysis with a balanced sample (4101 JAKi-treated and 5131 TNFi-treated patients), HR was 0.83 (95% CI 0.55 to 1.27) for overall malignancy: 0.77 (95% CI 0.50 to 1.19) for solid malignancy and 2.86 (95% CI 0.41 to 20.00) for haematological malignancy. CONCLUSION: Malignancy risk in Korean patients with RA was not increased with JAKi use compared with TNFi use.

Visuosocial Preference Memory, but Not Avoidance Memory, Requires PLCγ1 in the CA2 Hippocampus.

Visuosocial memory is defined as stored visual information containing social context. Primates have a powerful ability to associate visuosocial memory with episodic memory. However, the existence of visuosocial memory in mice remains unclear. Here, we design a novel vision-specific social memory test using a portrait picture or mirrored self-image and demonstrate that mice can distinguish conspecific from other species by forming a visuosocial memory. Because CA2 hippocampus has been reported as a critical brain region for social memory, we develop CA2-specific blockade of memory formation through deletion of phospholipase C gamma 1 (PLCγ1), which is a key molecule in the brain-derived neurotrophic factor (BDNF) signaling pathway. Interestingly, these mice have intact sociability but impaired social memory in three chamber test and five-trial social memory test, which is highly dependent on visual information. Finally, PLCγ1 deletion in CA2 impairs visuosocial preference memory, but not avoidance memory, whereas non-social object recognition is intact. Our study proposes that mice have visuosocial memory, just as primates and humans.

General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents.

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head-fixed, anesthesia-dependent, and acute, limiting clinical translatability. Here, this work reports a general-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact-free stimulation and simultaneous neural recording. Using the general-purpose system, it can be observed that state-dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

A Timing-Based Split-Path Sensing Circuit for STT-MRAM.

Spin-transfer torque magnetoresistive random access memory (STT-MRAM) applications have received considerable attention as a possible alternative for universal memory applications because they offer a cost advantage comparable to that of a dynamic RAM with fast performance comparable to that of a static RAM, while solving the scaling issues faced by conventional MRAMs. However, owing to the decrease in supply voltage (VDD) and increase in process fluctuations, STT-MRAMs require an advanced sensing circuit (SC) to ensure a sufficient read yield in deep submicron technology. In this study, we propose a timing-based split-path SC (TSSC) that can achieve a greater read yield compared to a conventional split-path SC (SPSC) by employing a timing-based dynamic reference voltage technique to minimize the threshold voltage mismatch effects. Monte Carlo simulation results based on industry-compatible 28-nm model parameters reveal that the proposed TSSC method obtains a 42% higher read access pass yield at a nominal VDD of 1.0 V compared to the SPSC in terms of iso-area and -power, trading off 1.75× sensing time.

Discordant vestibulo-ocular reflex function according to the frequency and mode of stimulation.

This study aimed to determine the incidence, pattern, and etiology of dissociated vestibulo-ocular reflex (VOR) function according to the stimulus frequency in dizzy patients. We retrospectively evaluated the results of bithermal caloric tests and video-head impulse tests (vHITs) in 1022 patients with dizziness or vertigo between July 2016 and April 2021. Patients were classified into concordant group (normal or abnormal results on both tests) and discordant group (dissociated results between two tests). Of 1022 patients, discordant group had 159 (16%), comprising abnormal horizontal vHITs with normal caloric responses (n = 36, 23%) and abnormal caloric tests with normal horizontal vHITs (n = 123, 77%). The former group showed similar frequency of peripheral (44%) and central (42%) causes, and more common involvement of bilateral horizontal semicircular canals in central than peripheral causes (86.7 vs 37.5%, p = 0.005). The most common peripheral causes were Meniere's disease and chronic vestibular neuritis, while central causes were variable, but mainly affecting the cerebellum. In the latter group, peripheral causes were common (67%), with the main etiologies being Meniere's disease and vestibular neuritis, whereas central causes were found in only 5%. The degree of canal paresis did not differ significantly between patients with central and peripheral causes. Discordant VOR function according to the stimulus frequency was not uncommon in dizzy patients. Specific patterns of VOR dissociation according to the disease etiologies may offer insight into underlying pathophysiology.

Erratum: Isolated Vestibular Syndrome With "Double-Panda" Sign in CNS Lymphoma.

This corrects the article on p. 111 in vol. 18, PMID: 35021288.

Can Corticomuscular Coherence Differentiate between REM Sleep Behavior Disorder with or without Parkinsonism?

REM sleep behavior disorder (RBD) could be a predictor of Parkinsonism even before development of typical motor symptoms. This study aims to characterize clinical features and corticomuscular and corticocortical coherence (CMC and CCC, respectively) during sleep in RBD patients with or without Parkinsonism. We enrolled a total of 105 subjects, including 20 controls, 54 iRBD, and 31 RBD+P patients, patients who were diagnosed as idiopathic RBD (iRBD) and RBD with Parkinsonism (RBD+P) in our neurology department. We analyzed muscle atonia index (MAI) and CMC between EEG and chin/limb muscle electromyography (EMG) and CCC during different sleep stages. Although differences in the CMC of iRBD group were observed only during REM sleep, MAI differences between groups were noted during both REM and NREM N2 stage sleep. During REM sleep, CMC was higher and MAI was reduced in iRBD patients compared to controls (p = 0.001, p < 0.001, respectively). Interestingly, MAI was more reduced in RBD+P compared to iRBD patients. In comparison, CCC was higher in iRBD patients compared to controls whereas CCC was lower in RBD+P groups compared to control and iRBD groups in various frequency bands during both NREM N2 and REM sleep stages. Among them, increased CMC during REM sleep revealed correlation between clinical severities of RBD symptoms. Our findings indicate that MAI, CMC, and CCC showed distinctive features in iRBD and RBD+P patients compared to controls, suggesting potential usefulness to understand possible links between these diseases.

Surface-Integrated Electric Field Sensor for the Detection of High-Voltage Power Lines.

When a drone is used for inspection of facilities, there are often cases in which high-voltage power lines interfere, resulting in the drone being caught or falling. To prevent this type of incident, drones must be capable of detecting high-voltage power lines. Typically, a strong electric field is formed around the high-voltage lines. To detect the electric fields around high-voltage lines, this study proposes an electric field sensor that may be integrated within the body of a drone. In a laboratory environment, a voltage of 25 kV was applied to an overhead line, and the induced voltage in the proposed sensor was measured at various electric field intensities. Over an electric field range of 0.5 to 10.1 kV/m, a voltage of 0 to 0.77 V was measured with each proposed sensor. In addition, the electric field and the voltage induced in the sensor were measured in a real-world railway environment with overhead lines. Under these conditions, the proposed sensor has the compensated value of 4.5 when the measured electric field was 4.05 kV/m. Therefore, the proposed sensor may be applied in drones to measure large electric fields and to detect the presence of high-voltage lines in its vicinity.

The Aftermath: Post-pandemic Psychiatric Implications of the COVID-19 Pandemic, a South Korean Perspective.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted our everyday life. Along with the fear of getting infected or of having loved ones infected, the lifestyle changes and the socioeconomic consequences of the pandemic have profound impact on mental health of the general population. While numerous studies on immediate psychological responses to COVID-19 are being published, there is a lack of discussion on its possible long-term sequelae. In this study, we systematically reviewed and meta-analyzed longitudinal studies that examined mental health of the general population prior to and during the pandemic. Furthermore, we explored the long-term psychiatric implications of the pandemic with data from South Korea. Our analysis showed that the number of suicidal deaths during the pandemic was lower than the previous years in many countries, which is in contrast with the increased depression, anxiety, and psychological distress in the general population in South Korea as well as in other countries. To explain this phenomenon, we propose a possibility of delayed impacts. The post-traumatic stress, long-term consequences of social restrictions, and maladaptive response to the "new normal" are discussed in the paper. COVID-19 being an unprecedented global crisis, more research and international collaboration are needed to understand, to treat, and to prevent its long-term effects on our mental health.

A study on the nutritional and biochemical analysis of Selaginella tamariscina powder.

This study reports the various nutritional components of Selaginella tamariscina, which is traditionally used in folk or Chinese medicine. The iron nutrient content in S. tamariscina powder was 0.94 ± 0.06 mg/100 g powder, whereas selenium was present in a small amount, which showed strong antioxidant power. The total phenolic content of S. tamariscina powder was 8.65-11.61 mg gallic acid equivalents/g. S. tamariscina showed antioxidant activity in 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The ferric reducing antioxidant power of S. tamariscina powder was higher in the ethanol extract. Additionally, the ethanol extract demonstrated antimicrobial activity against Bacillus subtilis KCTC 2189. The level of high-density lipoprotein-cholesterol in the blood of ICR mice was significantly higher in the HF 20% + S. tamariscina 20% group than in the other groups (p < 0.05). The present study demonstrates that S. tamariscina, an abundantly existing plant, possesses antimicrobial, antioxidant, and anticytotoxic activities. S. tamariscina powder has potential as a functional food.

A role of anterior cingulate cortex in the emergence of worker-parasite relationship.

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.