A transcriptional regulatory mechanism of genes in the tricarboxylic acid cycle in the heart.

The tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production in the healthy heart. However, in heart failure, the TCA cycle becomes dysregulated. Understanding the mechanism by which TCA cycle genes are transcribed in the healthy heart is an important prerequisite to understanding how these genes become dysregulated in the failing heart. PGC-1α is a transcriptional coactivator that broadly induces genes involved in mitochondrial ATP production. PGC-1α potentiates its effects through coactivation of coupled transcription factors, such as ERR, Nrf1, Gabpa, and YY1. We hypothesized that PGC-1α plays an essential role in transcription of TCA cycle genes. Thus, by utilizing localization peaks of PGC-1α to TCA cycle gene promoters, it would allow the identification of coupled transcription factors. PGC-1α potentiated the transcription of 13 out of 14 TCA cycle genes, partly through ERR, Nrf1, Gabpa, and YY1. ChIP-sequencing showed PGC-1α localization peaks in TCA cycle gene promoters. Transcription factors with binding elements that were found proximal to PGC-1α peak localization were generally essential for transcription of the gene. These transcription factor binding elements were well conserved between mice and humans. Among the four transcription factors, ERR and Gabpa played a major role in potentiating transcription when compared to Nrf1 and YY1. These transcription factor-dependent PGC-1α recruitment was verified with Idh3a, Idh3g, and Sdha promoters with DNA binding assay. Taken together, this study clarifies the mechanism by which TCA cycle genes are transcribed, which could be useful to understand how those genes are dysregulated in pathological conditions.

Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes.

While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.

Effects of plant- and animal-based-protein meals for a day on serum nitric oxide and peroxynitrite levels in healthy young men.

Plant-based diets that replace animal-based proteins with plant-based proteins have received increased attention for cardiovascular protection. Nitric oxide (NO) plays an essential role in the maintenance of endothelial function. However, under higher oxidative stress, NO generation produces peroxynitrite, a powerful oxidant and vasoconstrictor. Diet-replaced protein sources has been reported to decrease oxidative stress. However, the effects of plant-based protein on NO and peroxynitrite have not yet been clarified. Therefore, this study aimed to compare the effects of plant- and animal-based-protein meals for a day on NO, peroxynitrite, and NO/peroxynitrite balance. A crossover trial of two meal conditions involving nine healthy men was performed. Participants ate standard meals during day 1. On day 2, baseline measurements were performed and the participants were provided with plant-based-protein meals or animal-based-protein meals. The standard and test meals consisted of breakfast, lunch, and dinner and were designed to be isocaloric. Plant-based-protein meals contained no animal protein. Blood samples were collected in the morning after overnight fasting before and after the test meals consumption. In the plant-based-protein meal condition, serum NOx levels (the sum of serum nitrite and nitrate) significantly increased, while serum peroxynitrite levels did not change significantly. Animal-based-protein meals significantly increased serum peroxynitrite levels but showed a trend of reduction in the serum NOx levels. Furthermore, serum NO/peroxynitrite balance significantly increased after plant-based-protein meals consumption, but significantly decreased after animal-based-protein meals consumption. These results suggest that, compared with animal-based-protein meals, plant-based-protein meals increase NO levels and NO/peroxynitrite balance, which reflects increased endothelial function.

Iconicity mediates semantic networks of sound symbolisma).

One speech sound can be associated with multiple meanings through iconicity, indexicality, and/or systematicity. It was not until recently that this "pluripotentiality" of sound symbolism attracted serious attention, and it remains uninvestigated how pluripotentiality may arise. In the current study, Japanese, Korean, Mandarin, and English speakers rated unfamiliar jewel names on three semantic scales: size, brightness, and hardness. The results showed language-specific and cross-linguistically shared pluripotential sound symbolism. Japanese speakers associated voiced stops with large and dark jewels, whereas Mandarin speakers associated [i] with small and bright jewels. Japanese, Mandarin, and English speakers also associated lip rounding with darkness and softness. These sound-symbolic meanings are unlikely to be obtained through metaphorical or metonymical extension, nor are they reported to colexify. Notably, in a purely semantic network without the mediation of lip rounding, softness can instead be associated with brightness, as illustrated by synesthetic metaphors such as yawaraka-na hizashi /jawaɾakanaçizaɕi/ "a gentle (lit. soft) sunshine" in Japanese. These findings suggest that the semantic networks of sound symbolism may not coincide with those of metaphor or metonymy. The current study summarizes the findings in the form of (phono)semantic maps to facilitate cross-linguistic comparisons of pluripotential sound symbolism.

Dynamic Arterial Elastance as a Predictor of Supine-to-Prone Hypotension (SuProne Study): An Observational Study.

Background and Objectives: Supine-to-prone hypotension is caused by increased intrathoracic pressure and decreased venous return in the prone position. Dynamic arterial elastance (Eadyn) indicates fluid responsiveness and can be used to predict hypotension. This study aimed to investigate whether Eadyn can predict supine-to-prone hypotension. Materials and Methods: In this prospective, observational study, 47 patients who underwent elective spine surgery in the prone position were enrolled. Supine-to-prone hypotension is defined as a decrease in Mean Arterial Pressure (MAP) by more than 20% in the prone position compared to the supine position. Hemodynamic parameters, including systolic blood pressure (SAP), diastolic blood pressure, MAP, stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index, cardiac index, dP/dt, and hypotension prediction index (HPI), were collected in the supine and prone positions. Supine-to-prone hypotension was also assessed using two different definitions: MAPprone < 65 mmHg and SAPprone < 100 mmHg. Hemodynamic parameters were analyzed to determine the predictability of supine-to-prone hypotension. Results: Supine-to-prone hypotension occurred in 13 (27.7%) patients. Eadyn did not predict supine-to-prone hypotension [Area under the curve (AUC), 0.569; p = 0.440]. SAPsupine > 139 mmHg (AUC, 0.760; p = 0.003) and dP/dtsupine > 981 mmHg/s (AUC, 0.765; p = 0.002) predicted supine-to-prone hypotension. MAPsupine, SAPsupine, PPVsupine, and HPIsupine predicted MAPprone <65 mm Hg. MAPsupine, SAPsupine, SVVsupine, PPVsupine, and HPIsupine predicted SAPprone < 100 mm Hg. Conclusions: Dynamic arterial elastance did not predict supine-to-prone hypotension in patients undergoing spine surgery. Systolic arterial pressure > 139 mmHg and dP/dt > 981 mmHg/s in the supine position were predictors for supine-to-prone hypotension. When different definitions were employed (mean arterial pressure < 65 mmHg in the prone position or systolic arterial pressure < 100 mmHg in the prone position), low blood pressures in the supine position were related to supine-to-prone hypotension.

The ontogenesis and heterogeneity of basophils.

Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and some cancers. For years, the clinical significance of basophils has been neglected because of the lack of proper experimental tools to study them. The development of basophil-specific antibodies and animal models, along with genomic advances like single-cell transcriptomics, has greatly enhanced our understanding of basophil biology. Recent discoveries regarding basophils prompted us to write this review, emphasizing the basophil developmental pathway. In it, we chronologically examine the steps of basophil development in various species, which reveals the apparent advent of basophils predating IgE and basophil's IgE-independent regulatory role in primitive vertebrates. Then, we cover studies of basophil development in adult bone marrow, and compare those of murine and human basophils, introducing newly identified basophil progenitors and mature basophil subsets, as well as the transcription factors that regulate the transitions between them. Last, we discuss the heterogeneity of tissue-resident basophils, which may develop through extramedullary hematopoiesis. We expect that this review will contribute to a deeper understanding of basophil biology from the intricate aspects of basophil development and differentiation, offering valuable insights for both researchers and clinicians.

GSK4716 enhances 5-HT1AR expression by glucocorticoid receptor signaling in hippocampal HT22 cells.

OBJECTIVES: The serotonin (5-hydroxytryptamine, 5-HT) receptor 1A (5-HT1AR) is closely associated with serotonergic neurotransmission in the brain, being the most prevalent and widely distributed receptor of its kind. The purpose of this study is to investigate the regulation mechanism of 5-HT1AR by GSK4716. METHODS: To investigate the mechanism of GSK4716-mediated 5-HT1AR regulation, we used hippocampus-derived HT22 cells expressing 5-HT1AR. The expression level of 5-HT1AR and associated proteins, were detected by reporter gene assay and western blotting. RESULTS: GSK4716, an estrogen-related receptor gamma agonist increased 5-HT1AR expression by interacting with the GR, a repressor of 5-HT1AR transcription. Dexamethasone, a GR agonist, decreased the GSK4716-induced increase in 5-HT1AR, which was associated with an alteration in nuclear GR. Furthermore, GR antagonist RU486 reversed the effects induced by dexamethasone, including the elevation of nuclear GR levels and the reduction of 5-HT1AR transcription and expression. CONCLUSION: The results could provide insight into the potential applications of small molecules, such as GSK4716, in the regulation of 5-HT1AR expression, which plays a role in serotonergic neurotransmission.

The landscape of decentralized clinical trials (DCTs): focusing on the FDA and EMA guidance.

Decentralized clinical trials (DCTs) consist of off-site trial-related procedures referred to as decentralized elements. We aimed to provide an overview of the landscape of DCTs by comparing regulatory guidance reports and analyzing decentralized elements from clinical trial registries. Two guidance reports on DCTs published by the U.S. Food and Drug Administration and the European Medicines Agencies were summarized and analyzed. Both guidance publications commonly emphasized an assessment of the appropriateness of decentralized elements along 2 axes: patient safety and data integrity. DCT cases were identified from ClinicalTrials.gov by searching with 6 keywords: decentralized, remote, mobile, digital, virtual, and hybrid. Cases where the keyword was used in a non-DCT context, such as digital flexor tendon, were excluded by means of natural language processing. A total of 4,874 trials were identified as DCT cases, with annual increases, especially after 2020. The most common keywords were 'mobile' and 'digital' (36.2% and 24.8%, respectively). Interventions in the DCT cases were analyzed by means of a network analysis. Behavioral and technological tokens were frequently combined, such as 'rehabilitation' and 'app.' Drugs were used in only 1.8% of the DCT cases. Of these, most drugs had been approved previously (96.8%) and were in oral formulation (67.2%). Most of the DCT cases identified in this study involved simple interventions and low-risk drugs. These characteristics were in accordance with the common recommendations in the DCT guidance publications.

RPS24 alternative splicing is a marker of cancer progression and epithelial-mesenchymal transition.

Although alternative splicing (AS) is a major mechanism that adds diversity to gene expression patterns, its precise role in generating variability in ribosomal proteins, known as ribosomal heterogeneity, remains unclear. The ribosomal protein S24 (RPS24) gene, encoding a ribosomal component, undergoes AS; however, in-depth studies have been challenging because of three microexons between exons 4 and 6. We conducted a detailed analysis of RPS24 AS isoforms using a direct approach to investigate the splicing junctions related to these microexons, focusing on four AS isoforms. Each of these isoforms showed tissue specificity and relative differences in expression among cancer types. Significant differences in the proportions of these RPS24 AS isoforms between cancerous and normal tissues across diverse cancer types were also observed. Our study highlighted a significant correlation between the expression levels of a specific RPS24 AS isoform and the epithelial-mesenchymal transition process in lung and breast cancers. Our research contributes to a better understanding of the intricate regulatory mechanisms governing AS of ribosomal protein genes and highlights the biological implications of RPS24 AS isoforms in tissue development and tumorigenesis.

Establishment of Advanced Regulatory Innovation for Clinical Trials Transformation (ARICTT): a multi-stakeholder public-private partnership-based organization to accelerate the transformation of clinical trials.

Clinical trials have evolved with digital technologies and tend towards patient-centricity. A multi-stakeholder approach is needed to address the emerging complexities in clinical trials. In particular, the introduction of digital technologies and an emphasis on patient-centricity are the major trends in clinical trials. In response, we established a public-private partnership-based organization named Advanced Regulatory Innovation for Clinical Trials Transformation (ARICTT). Eleven organizations in total, from academia, industry, and regulatory agencies, participate in ARICTT. Based on multi-stakeholder collaboration from academia, industry, and government/regulatory bodies, we collected and prioritized current topics in clinical trials based on an internal survey. We established a three-year roadmap with axes that were termed trend, goal, structure, theme, topic, and method. In addition, we planned the development of recommendations based on real-world cases with feasibility studies. We developed appropriate organizational structure to fulfill the roadmap of ARICTT. The selected topics were decentralized clinical trials during the first year, followed by the three topics that were awarded the highest priority according to the internal survey: advances in the informed consent process, supporting sites using digital technology, and an effective recruitment strategy. We developed a case-based recommendation paper presenting an overview of the regulatory landscape and practical considerations with explanatory cases. We also designed and conducted fully decentralized trials to evaluate considerations in real-world settings for the selected topics. Overall engagement and communication were supported by the online platform and annual symposiums. In conclusion, we established a multi-stakeholder, public-private partnership-based organization to accelerate the transformation of clinical trials.

Fungal Diversity in Nam River and Their Biodegradative Activities.

145 fungal isolates were obtained from three sampling sites situated within the Nam River basin, located in the southern region of South Korea. Through ITS sequence analysis, the fungal isolates were identified to comprise 55 species of ascomycetes and 11 species of basidiomycetes. The 55 species of ascomycetes exclusively belong to the phylum Pezizomycotina, comprising 33 species of Dothideomycetes, 6 species of Eurotiomycetes, and 16 species of Sordariomycetes. Regarding their plant pathogenicity, an investigation into the fungi's ability to penetrate solid media revealed Nigrospora chinensis as displaying the highest growth, followed by Pseudopestalotiopsis theae, various Curvularia species, Diaporthe species, and Alternaria alternata. Further research associating this penetration ability with fungal pathogenicity is deemed necessary. Among the 10 fungal species exhibiting penetration abilities, an examination of their capability to degrade biological polymers revealed that two strains of D. phaseolorum displayed exceptional polymer degradation. These strains exhibited remarkable abilities in decomposing malachite green and crystal violet, both recalcitrant dyes. This study underscores the potential utilization of fungal diversity in freshwater environments as a foundational approach to address freshwater pollution issues.

Potential Therapeutic Improvements in Prostate Cancer Treatment Using Pencil Beam Scanning Proton Therapy with LETd Optimization and Disease-Specific RBE Models.

PURPOSE: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. METHODS: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose-volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. RESULTS: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. CONCLUSION: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes.

Exploring the Correlation between Systemic Inflammatory Markers and Carotid Atherosclerosis Indices in Middle-Aged Adults: A Cross-Sectional Study.

BACKGROUND: This study investigated the association between atherosclerosis and systemic inflammation markers, specifically the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in healthy middle-aged adults. METHODS: A retrospective cross-sectional study was conducted on a total of 1264 Korean adults aged 40-65. We assessed these inflammatory markers and carotid metrics, such as carotid intima-media thickness (cIMT), plaque number (PN), plaque stenosis score (PSS), and plaque score (PS), using linear regression, logistic regression, and receiver operating characteristic analysis. RESULTS: In males, the ESR and CRP were significantly correlated with the PN (p < 0.001 and p = 0.048, respectively). The ESR was correlated with the PN in females (p = 0.004). The NLR and PLR both correlated with the PS in males (p < 0.001 and p = 0.015, respectively) and females (p = 0.015 and p = 0.023, respectively). The odds ratio for the NLR as a risk factor for increased cIMT was 1.15 (95% confidence interval [CI], 1.03-2.15) for males and 1.05 (95% CI, 1.01-1.29) for females. The AUC for the NLR and PLR as a predictor for the PS showed significance in both men and women. CONCLUSIONS: Inflammatory markers, particularly the NLR and PLR, demonstrate a correlation with carotid atherosclerosis. Both the NLR and PLR hold potential as valuable surrogate markers for carotid atherosclerosis. To further substantiate their predictive efficacy, further prospective studies are needed.

Impact of Plant and Animal Protein-Based Meals on Serum Fibroblast Growth Factor-23 Levels in Healthy Young Men: A Randomized Crossover Trial.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons. This randomized crossover trial aimed to determine the potential differences in the impacts on serum FGF23 levels between plant protein and animal protein-based meals in individuals with normal renal function. Nine young men were administered plant (no animal protein) or animal protein-based meals (70% of their protein was from animal sources) with the same phosphate content. The test meals consisted of breakfast, lunch, and dinner. Blood samples were collected in the morning, after overnight fasting, and before and after eating the test meals (for two consecutive days at the same hour each day). Furthermore, a 24-h urine sample was obtained on the day the test meal was consumed. No significant interactions were found among serum phosphate, calcium, and 1,25-dihydroxyvitamin D levels. However, after eating plant protein-based meals, serum FGF23 levels decreased and serum intact parathyroid hormone levels increased (interaction, p<0.05). Additionally, urine 24-h phosphate excretion tended to be lower in individuals consuming plant protein-based meals than in those consuming animal protein-based meals (p=0.06). In individuals with normal renal function, plant protein-based meals may prevent an increase in serum FGF23 levels and kidney damage caused by phosphate loading.

Navigating Complexities: Leadless Pacemaker Management in Proton Therapy for a Pacemaker-Dependent Bilateral Breast Cancer Patient.

This case study explores the strategic decision-making and safety considerations in managing a unique scenario where a pacemaker dependent patient, requiring adjuvant radiotherapy for bilateral breast cancer. The conventional pacemaker was located entirely within the treatment target, without the option for transposition because of the bilateral chest treatment, resulting in significant risk of malfunction caused by exposing it to the full prescribed dose. Consequently, the decision was made to replace the conventional pacemaker with a leadless device Micra implanted directly into the heart to mitigate direct device radiation and potential adverse effects of proton therapy on the cardiac device. Following Micra implantation, the patient underwent the proton treatment without complications or serious device malfunctions. This study explores solutions to address the challenges posed by within-the-field cardiac devices and highlights the use of pencil beam proton therapy for individuals with leadless cardiac devices while acknowledging the potential for neutron production and the associated risk of single-event upsets (SEU) in cardiac implantable electronic devices (CIEDs). The findings underscore the significance of strategic decision-making, risk assessment, and continuous monitoring for successful outcomes, particularly in the context of proton therapy for patients with advanced cardiac considerations.

Comparative study on the impact of remimazolam and sevoflurane on quality of recovery after transurethral resection of bladder tumor: A randomized controlled noninferiority study.

BACKGROUND: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane. METHODS: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed. RESULTS: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032). CONCLUSION: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane.

Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial.

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and ß-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Nefopam as a multimodal analgesia in thoracoscopic surgery: a randomized controlled trial.

Background: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. However, some patients still experience severe pain after VATS. Pain after VATS can disturb deep breathing and coughing, and can increase postoperative pulmonary complications. Therefore, multidisciplinary pain management is emphasized for enhanced recovery after VATS. Nefopam is a centrally-acting, non-opioid, non-steroidal analgesic drug, and its pain reduction effect in many surgeries has been reported. We sought to determine whether administration of nefopam is effective as multimodal analgesia in VATS. Methods: This study enrolled patients aged 19 years or older, and scheduled for elective VATS lobectomy with American Society of Anesthesiologists (ASA) physical class I-III. Forty-six participants were randomly divided into a group receiving nefopam (group N), and a control group (group O) in a 1:1 ratio. The study participants, and the researcher collecting the data were blinded to the group allocation. For the group N, nefopam 20 mg was administered before surgical incision and also at the end of surgery while chest tube was inserted. For the group O, normal saline 100 mL was administered. The primary outcome of this study was the pain score, by verbal numerical rating scale, at rest and upon coughing. Results: Forty-five participants (group N =22, group O =23) were involved in the statistical analysis. Nefopam reduced pain at rest at 0 h [8 (IQR, 5-10) vs. 4 (IQR, 2-7), P=0.01], and at 0-1 h [5 (IQR, 5-8) vs. 3 (IQR, 2-5), P=0.001]. Pain upon coughing decreased with nefopam at 0 h [9 (IQR, 6-10) vs. 6 (IQR, 2-8), P=0.009], 0-1 h [6 (IQR, 5-8) vs. 5 (IQR, 2-6), P=0.001], and at 12-24 h [4 (IQR, 3-7) vs. 3 (IQR, 1-4), P=0.03]. Injection of 20 mg of nefopam before incision and at the end of surgery relieved postoperative pain at 0 h, 1 h at rest and at 0 h, 1 h, 12-24 h with coughing after VATS. Conclusions: Therefore, nefopam can serve as a useful component of multimodal analgesia for pain management after VATS. Trial Registration: ClinicalTrials.gov (NCT05173337).

Draft genome sequence of multiple antibiotic-resistant Vibrio harveyi isolated from diseased olive flounder (Paralichthys olivaceus) farmed in South Korea.

Vibrio harveyi strain 22FBVib0145 was isolated from a diseased olive flounder farmed in Jeju, Korea. Here, we report the draft genome sequence of this strain. It is 6,238,277 bp in length with a G + C content of 44.8%.

Effect of modification methods on the physical properties and immunomodulatory activity of particulate ß-glucan.

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.