Integrative Analysis of Probiotic-Mediated Remodeling in Canine Gut Microbiota and Metabolites Using a Fermenter for an Intestinal Microbiota Model.

In contemporary society, the increasing number of pet-owning households has significantly heightened interest in companion animal health, expanding the probiotics market aimed at enhancing pet well-being. Consequently, research into the gut microbiota of companion animals has gained momentum, however, ethical and societal challenges associated with experiments on intelligent and pain-sensitive animals necessitate alternative research methodologies to reduce reliance on live animal testing. To address this need, the Fermenter for Intestinal Microbiota Model (FIMM) is being investigated as an in vitro tool designed to replicate gastrointestinal conditions of living animals, offering a means to study gut microbiota while minimizing animal experimentation. The FIMM system explored interactions between intestinal microbiota and probiotics within a simulated gut environment. Two strains of commercial probiotic bacteria, Enterococcus faecium IDCC 2102 and Bifidobacterium lactis IDCC 4301, along with a newly isolated strain from domestic dogs, Lactobacillus acidophilus SLAM AK001, were introduced into the FIMM system with gut microbiota from a beagle model. Findings highlight the system's capacity to mirror and modulate the gut environment, evidenced by an increase in beneficial bacteria like Lactobacillus and Faecalibacterium and a decrease in the pathogen Clostridium. The study also verified the system's ability to facilitate accurate interactions between probiotics and commensal bacteria, demonstrated by the production of short-chain fatty acids and bacterial metabolites, including amino acids and gamma-aminobutyric acid precursors. Thus, the results advocate for FIMM as an in vitro system that authentically simulates the intestinal environment, presenting a viable alternative for examining gut microbiota and metabolites in companion animals.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

Claude 3 Opus and ChatGPT With GPT-4 in Dermoscopic Image Analysis for Melanoma Diagnosis: Comparative Performance Analysis.

BACKGROUND: Recent advancements in artificial intelligence (AI) and large language models (LLMs) have shown potential in medical fields, including dermatology. With the introduction of image analysis capabilities in LLMs, their application in dermatological diagnostics has garnered significant interest. These capabilities are enabled by the integration of computer vision techniques into the underlying architecture of LLMs. OBJECTIVE: This study aimed to compare the diagnostic performance of Claude 3 Opus and ChatGPT with GPT-4 in analyzing dermoscopic images for melanoma detection, providing insights into their strengths and limitations. METHODS: We randomly selected 100 histopathology-confirmed dermoscopic images (50 malignant, 50 benign) from the International Skin Imaging Collaboration (ISIC) archive using a computer-generated randomization process. The ISIC archive was chosen due to its comprehensive and well-annotated collection of dermoscopic images, ensuring a diverse and representative sample. Images were included if they were dermoscopic images of melanocytic lesions with histopathologically confirmed diagnoses. Each model was given the same prompt, instructing it to provide the top 3 differential diagnoses for each image, ranked by likelihood. Primary diagnosis accuracy, accuracy of the top 3 differential diagnoses, and malignancy discrimination ability were assessed. The McNemar test was chosen to compare the diagnostic performance of the 2 models, as it is suitable for analyzing paired nominal data. RESULTS: In the primary diagnosis, Claude 3 Opus achieved 54.9% sensitivity (95% CI 44.08%-65.37%), 57.14% specificity (95% CI 46.31%-67.46%), and 56% accuracy (95% CI 46.22%-65.42%), while ChatGPT demonstrated 56.86% sensitivity (95% CI 45.99%-67.21%), 38.78% specificity (95% CI 28.77%-49.59%), and 48% accuracy (95% CI 38.37%-57.75%). The McNemar test showed no significant difference between the 2 models (P=.17). For the top 3 differential diagnoses, Claude 3 Opus and ChatGPT included the correct diagnosis in 76% (95% CI 66.33%-83.77%) and 78% (95% CI 68.46%-85.45%) of cases, respectively. The McNemar test showed no significant difference (P=.56). In malignancy discrimination, Claude 3 Opus outperformed ChatGPT with 47.06% sensitivity, 81.63% specificity, and 64% accuracy, compared to 45.1%, 42.86%, and 44%, respectively. The McNemar test showed a significant difference (P<.001). Claude 3 Opus had an odds ratio of 3.951 (95% CI 1.685-9.263) in discriminating malignancy, while ChatGPT-4 had an odds ratio of 0.616 (95% CI 0.297-1.278). CONCLUSIONS: Our study highlights the potential of LLMs in assisting dermatologists but also reveals their limitations. Both models made errors in diagnosing melanoma and benign lesions. These findings underscore the need for developing robust, transparent, and clinically validated AI models through collaborative efforts between AI researchers, dermatologists, and other health care professionals. While AI can provide valuable insights, it cannot yet replace the expertise of trained clinicians.

Endoscopic findings of immune checkpoint inhibitor-related gastrointestinal adverse events.

The use of immune checkpoint inhibitors (ICIs) for the treatment of various malignancies is increasing. Immune-related adverse events can occur after ICI administration, with gastrointestinal adverse events constituting a significant proportion of these events. When ICI-related diarrhea/colitis is suspected, endoscopic evaluation is recommended to differentiate it from other etiologies and assess the severity of colitis. The distribution of intestinal inflammation in ICI-related colitis demonstrates a high frequency of extensive colitis (23-86%). However, isolated right-sided colitis (3-8%) and ileitis (2-16%) are less prevalent. Endoscopic findings vary and predominantly encompass features indicative of inflammatory bowel disease, including aphthae, ulcers, diffuse or patchy erythema, mucosal edema, loss of vascular pattern, and friability. The presence of ulcers and extensive intestinal inflammation are associated with a reduced response to treatment. Microscopic inflammation can be observed even in endoscopically normal mucosa, underscoring the need for biopsies of seemingly normal mucosa. Histological findings present with acute/chronic inflammation and occasionally exhibit characteristics observed in inflammatory bowel disease, microscopic colitis, or ischemic colitis. The first-line therapeutic choice for ICI-related diarrhea/colitis with a common terminology criteria for adverse events grade of 2 or above is corticosteroids, whereas infliximab and vedolizumab are recommended for refractory cases.

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis.

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

ARHGEF5 binds Drebrin and affects α-tubulin acetylation to direct neuronal morphogenesis and migration during mouse brain development.

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5's role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

Nuclear factor κB overactivation in the intervertebral disc leads to macrophage recruitment and severe disc degeneration.

Persistent inflammation has been associated with severe disc degeneration (DD). This study investigated the effect of prolonged nuclear factor κB (NF-κB) activation in DD. Using an inducible mouse model, we genetically targeted cells expressing aggrecan, a primary component of the disc extra cellular matrix, for activation of the canonical NF-κB pathway. Prolonged NF-κB activation led to severe structural degeneration accompanied by increases in gene expression of inflammatory molecules (Il1b, Cox2, Il6, and Nos2), chemokines (Mcp1 and Mif), and catabolic enzymes (Mmp3, Mmp9, and Adamts4). Increased recruitment of proinflammatory (F4/80+,CD38+) and inflammatory resolving (F4/80+,CD206+) macrophages was observed within caudal discs. We found that the secretome of inflamed caudal disc cells increased macrophage migration and inflammatory activation. Lumbar discs did not exhibit phenotypic changes, suggestive of regional spinal differences in response to inflammatory genetic overactivation. Results suggest prolonged NF-κB activation can induce severe DD through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and activation of macrophage cell populations.

Effects of subcutaneous drain on wound dehiscence and infection in gynecological midline laparotomy: Secondary analysis of a Korean Gynecologic Oncology Group study (KGOG 4001).

OBJECTIVE: To identify the effects of subcutaneous drain insertion on wound dehiscence and infection in patients who underwent gynecological midline laparotomy. METHODS: This analysis identified the secondary endpoints of the KGOG 4001 study, a prospective, multicenter, non-blind, randomized controlled trial. Patients scheduled to undergo midline laparotomy for gynecological diseases and, with body mass index<35 kg/m2, were randomized (1:1) to treatment (with subcutaneous drain) and control (without subcutaneous drain) groups from February 2021 to December 2021. We compared the incidence rate of wound dehiscence 4 weeks post-surgery and the cumulative incidence rate of wound dehiscence and infection up to 4 weeks post-surgery between the two groups. RESULTS: Of 174 patients randomized to the treatment (n = 84) and control (n = 90) groups, 12 were excluded owing to loss to follow-up; finally, 162 patients (treatment, n = 79; control, n = 83) were included in intention-to-treat analysis. The frequency of cancer surgery (79.7 % vs. 77.1 %, p = 0.683), mean surgery time (227.7 vs. 226.7 min, p = 0.960), and mean wound length (24.2 vs. 24.3 cm, p = 0.933) were comparable between two groups. No significant differences were observed in the incidence rate of wound dehiscence 4 weeks post-surgery (1.3 % vs. 2.4 %, p > 0.999), cumulative incidence rate of wound dehiscence (8.9 % vs. 6.0 %, p = 0.491), and cumulative incidence rate of wound infection (1.3 % vs. 0.0 %, p = 0.488) up to 4 weeks post-surgery between the two groups. CONCLUSION: Subcutaneous drain insertion is not associated with a significant improvement in the incidence of wound dehiscence and infection in patients who undergo gynecological midline laparotomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643197.

A novel APP splice variant-dependent marker system to precisely demarcate maturity in SH-SY5Y cell-derived neurons.

SH-SY5Y, a neuroblastoma cell line, can be converted into mature neuronal phenotypes, characterized by the expression of mature neuronal and neurotransmitter markers. However, the mature phenotypes described across multiple studies appear inconsistent. As this cell line expresses common neuronal markers after a simple induction, there is a high chance of misinterpreting its maturity. Therefore, sole reliance on common neuronal markers is presumably inadequate. The Alzheimer's disease (AD) central gene, amyloid precursor protein (APP), has shown contrasting transcript variant dynamics in various cell types. We differentiated SH-SY5Y cells into mature neuron-like cells using a concise protocol and observed the upregulation of total APP throughout differentiation. However, APP transcript variant-1 was upregulated only during the early to middle stages of differentiation and declined in later stages. We identified the maturity state where this post-transcriptional shift occurs, terming it "true maturity." At this stage, we observed a predominant expression of mature neuronal and cholinergic markers, along with a distinct APP variant pattern. Our findings emphasize the necessity of using a differentiation state-sensitive marker system to precisely characterize SH-SY5Y differentiation. Moreover, this study offers an APP-guided, alternative neuronal marker system to enhance the accuracy of the conventional markers.

Floating electrode-dielectric barrier discharge-based plasma promotes skin regeneration in a full-thickness skin defect mouse model.

Wound healing involves a complex and dynamic interplay among various cell types, cytokines, and growth factors. Macrophages and transforming growth factor-ß1 (TGF-ß1) play an essential role in different phases of wound healing. Cold atmospheric plasma has a wide range of applications in the treatment of chronic wounds. Hence, we aimed to investigate the safety and efficacy of a custom-made plasma device in a full-thickness skin defect mouse model. Here, we investigated the wound tissue on days 6 and 12 using histology, qPCR, and western blotting. During the inflammation phase of wound repair, macrophages play an important role in the onset and resolution of inflammation, showing decreased F4/80 on day 6 of plasma treatment and increased TGF-ß1 levels. The plasma-treated group showed better epidermal epithelialization, dermal fibrosis, collagen maturation, and reduced inflammation than the control group. Our findings revealed that floating electrode-dielectric barrier discharge (FE-DBD)-based atmospheric-pressure plasma promoted significantly faster wound healing in the plasma-treated group than that in the control group with untreated wounds. Hence, plasma treatment accelerated wound healing processes without noticeable side effects and suppressed pro-inflammatory genes, suggesting that FE-DBD-based plasma could be a potential therapeutic option for treating various wounds.

Transient receptor potential vanilloid 4 regulates extracellular matrix composition and mediates load-induced intervertebral disc degeneration in a mouse model.

OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) is a multi-modally activated cation channel that mediates mechanotransduction pathways by which musculoskeletal tissues respond to mechanical load and regulate tissue health. Using conditional Trpv4 knockout mice, we investigated the role of Trpv4 in regulating intervertebral disc (IVD) health and injury-induced IVD degeneration. METHODS: Col2-Cre;Trpv4fl/f (Trpv4 KO) mice were used to knockout Trpv4 in all type 2 collagen-expressing cells. Effects of gene targeting alone was assessed in lumbar spines, using vertebral bone length measurement, histological, immunohistochemistry and gene expression analyses, and mechanical testing. Disc puncture was performed on caudal IVDs of wild-type (WT) and Trpv4 KO mice at 2.5- and 6.5-months-of-age. Six weeks after puncture (4- and 8-months-of-age at sacrifice), caudal spines were assessed using histological analyses. RESULTS: While loss of Trpv4 did not significantly alter vertebral bone length and tissue histomorphology compared to age-matched WT mice, Trpv4 KO mice showed decreased proteoglycan and PRG4 staining in the annulus fibrosus compared to WT. At the gene level, Trpv4 KO mice showed significantly increased expression of Acan, Bgn, and Prg4 compared to WT. Functionally, loss of Trpv4 was associated with significantly increased neutral zone length in lumbar IVDs. Following puncture, both Trpv4 KO and WT mice showed similar signs of degeneration at the site of injury. Interestingly, loss of Trpv4 prevented mechanically-induced degeneration in IVDs adjacent to sites of injury. CONCLUSION: These studies suggest a role for Trpv4 in regulating extracellular matrix synthesis and mediating the response of IVD tissues to mechanical stress.

Comparison between Onyx and coil embolization for persistent type 2 endoleaks after endovascular aneurysm repair.

Purpose: Type 2 endoleaks (T2EL) are the most common form of endoleaks after endovascular aneurysm repair (EVAR). Several studies on the feasibility of embolization using ethylene vinyl alcohol copolymer (Onyx, Medtronic) for T2EL have been reported. The purpose of this study was to compare coil and Onyx embolization for T2EL treatment after EVAR. Methods: Between August 2005 and July 2022, 46 patients underwent endovascular embolization for treatment of T2EL (15 Onyx and 31 coils). The primary endpoint was endoleaks resolution or significant aneurysm sac growth of >5 mm in maximal diameter after T2EL embolization. In addition, periprocedural factors, reintervention, sac rupture, and survival analysis were assessed. Results: The follow-up period after embolization was significantly shorter in the Onyx group (11.6 months vs. 34.7 months, P = 0.016), and there was no difference in aneurysm sac growth rate between both groups (20.0% vs. 51.6%; P = 0.472, log-rank test). However, cases with multiple endoleak origins tended to be treated with Onyx (P = 0.002). When applying Onyx, there was no significant difference in results between the transarterial and translumbar approaches. Conclusion: There appears to be no significant difference in the results of Onyx and coil embolization for T2EL treatment, although it is difficult to evaluate effectiveness due to the small number of cases and short follow-up period. However, in cases of multiple origin endoleaks or when the transarterial approach is not feasible, the Onyx by translumbar approach may be a more effective method.

Assessment of the Reliability and Clinical Applicability of ChatGPT's Responses to Patients' Common Queries About Rosacea.

Objective: Artificial intelligence chatbot, particularly ChatGPT (Chat Generative Pre-trained Transformer), is capable of analyzing human input and generating human-like responses, which shows its potential application in healthcare. People with rosacea often have questions about alleviating symptoms and daily skin-care, which is suitable for ChatGPT to response. This study aims to assess the reliability and clinical applicability of ChatGPT 3.5 in responding to patients' common queries about rosacea and to evaluate the extent of ChatGPT's coverage in dermatology resources. Methods: Based on a qualitative analysis of the literature on the queries from rosacea patients, we have extracted 20 questions of patients' greatest concerns, covering four main categories: treatment, triggers and diet, skincare, and special manifestations of rosacea. Each question was inputted into ChatGPT separately for three rounds of question-and-answer conversations. The generated answers will be evaluated by three experienced dermatologists with postgraduate degrees and over five years of clinical experience in dermatology, to assess their reliability and applicability for clinical practice. Results: The analysis results indicate that the reviewers unanimously agreed that ChatGPT achieved a high reliability of 92.22% to 97.78% in responding to patients' common queries about rosacea. Additionally, almost all answers were applicable for supporting rosacea patient education, with a clinical applicability ranging from 98.61% to 100.00%. The consistency of the expert ratings was excellent (all significance levels were less than 0.05), with a consistency coefficient of 0.404 for content reliability and 0.456 for clinical practicality, indicating significant consistency in the results and a high level of agreement among the expert ratings. Conclusion: ChatGPT 3.5 exhibits excellent reliability and clinical applicability in responding to patients' common queries about rosacea. This artificial intelligence tool is applicable for supporting rosacea patient education.

Evaluation of stability and safety of equine mesenchymal stem cells derived from amniotic fluid for clinical application.

Amniotic fluid mesenchymal stem cells (AF-MSCs), which can be obtained from fetal tissue, reportedly have self-renewal capacity and multi-lineage differentiation potential. The aim of this study was to identify the biological characteristics of AF-MSCs and evaluate their stability and safety in long-term culture. To confirm the biological characteristics of AF-MSCs, morphology, proliferation capacity, karyotype, differentiation capacity, gene expression level, and immunophenotype were analyzed after isolating AF-MSCs from equine amniotic fluid. AF-MSCs were differentiated into adipocytes, chondrocytes, and osteocytes. Immunophenotype analyses revealed expression levels of ≥95% and ≤ 2% of cells for a positive and negative marker, respectively. Analysis of the MSCs relative gene expression levels of AF-MSCs was approximately at least twice that of the control. The endotoxin level was measured to verify the safety of AF-MSCs and was found to be less than the standard value of 0.5 EU/ml. AF-MSCs were cultured for a long time without any evidence of abnormalities in morphology, proliferation ability, and karyotype. These results suggest that amniotic fluid is a competent source for acquiring equine MSCs and that it is valuable as a cell therapy due to its high stability.

Exploring the exponential sensitivity of risk perception in the COVID-19 pandemic.

Individual's risk perception regarding specific hazards is a dynamic process that evolves over time. This study analyzed the relationship between the number of COVID-19 cases and the South Korean public's risk perceptions from the outset of the pandemic to the recent past. More than 70 repeated cross-sectional surveys were conducted biweekly to measure individuals' risk perception. An autoregressive integrated moving average with explanatory variable time series analysis was used to characterize the relationship between the number of COVID-19 cases and level of risk perceptions. It revealed that individuals' risk perception and the number of COVID-19 cases were not linearly related but were logarithmically correlated. This finding can be understood as a psychic numbing effect, suggesting that people's perception of risk is not linear but rather exponentially sensitive to changes. The findings also revealed a significant influence of individuals' trust in local governments on their risk perceptions, highlighting the substantial role played by local governments in direct risk management during the COVID-19 pandemic.

Myomectomy with ArtiSential fully articulating laparoscopic instruments: A prospective multicenter study.

BACKGROUND: ArtiSential, a class of innovative laparoscopic instrument, has been developed to overcome the limitations of conventional laparoscopic surgery by enabling free, 360°-unrestricted movement of the wrist joint, as in robotic surgery. OBJECTIVE: The aim of the present study was to describe the initial experiences with these devices in myomectomy and to report the surgical outcomes. METHODS: A total of 77 women undergoing laparoscopic or robotic myomectomy between January 2021 and June 2022 were included in this multicenter prospective study. The ArtiSential instruments used by the surgeons were those chosen according to their respective preferences. The baseline characteristics, surgical outcomes, trocar placement options, and operator survey results were scrutinized. RESULTS: The mean age of the patients was 39.9 ± 6.3, and the mean body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was 22.4 ± 3.4 kg/m2; 46.8% of the patients underwent robotic surgery, while 53.2% underwent laparoscopic surgery. The number of removed myomas was 3.3 ± 3.0, the size of the largest myoma was 7.1 ± 2.3 cm, and the operative time was 130.0 ± 54.0 min. No transfusions or laparotomy conversions were required. Other than one case of ileus, there were no postoperative complications. In most cases, the instruments were inserted through the umbilicus trocar, and the fenestrated forceps, needle holder, and bipolar fenestrated forceps, in that order, were frequently employed. According to a surgeon survey, 29.9% moderately or strongly agreed that the ArtiSential devices utilized were more convenient than conventional laparoscopic instruments, while only 9.7% moderately or strongly agreed that they were more convenient than robotic instruments. CONCLUSIONS: Myomectomy as performed with an ArtiSential instrument seems to be feasible and safe. Further studies are necessary in order to comparatively assess the outcomes and potential benefits of ArtiSential, robotic, and conventional laparoscopic myomectomy.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Dietary supplementation with probiotics promotes weight loss by reshaping the gut microbiome and energy metabolism in obese dogs.

Obesity and overweight among companion animals are significant concerns, paralleling the issues observed in human populations. Recent research has highlighted the potential benefits of various probiotics in addressing weight-related changes, obesity, and associated pathologies. In this study, we delved into the beneficial probiotic mechanisms in high-fat-induced obese canines, revealing that Enterococcus faecium IDCC 2102 (IDCC 2102) and Bifidobacterium lactis IDCC 4301 (IDCC 4301) have the capacity to mitigate the increase in body weight and lipid accumulation in obese canines subjected to a high-fat diet and hyperlipidemic Caenorhabditis elegans (C. elegans) strain VS29. Both IDCC 2102 and IDCC 4301 demonstrated the ability to reduce systemic inflammation and hormonal disruptions induced by obesity. Notably, these probiotics induced modifications in the microbiota by promoting lactic acid bacteria, including Lactobacillaceae, Ruminococcaceae, and S24-7, with concomitant activation of pyruvate metabolism. IDCC 4301, through the generation of bacterial short-chain fatty acids and carboxylic acids, facilitated glycolysis and contributed to ATP synthesis. Meanwhile, IDCC 2102 produced bacterial metabolites such as acetic acid and butyric acid, exhibiting a particular ability to stimulate dopamine synthesis in a canine model. This stimulation led to the restoration of eating behavior and improvements in glucose and insulin tolerance. In summary, we propose novel probiotics for the treatment of obese animals based on the modifications induced by IDCC 2102 and IDCC 4301. These probiotics enhanced systemic energy utilization in response to high caloric intake, thereby preventing lipid accumulation and restoring stability to the fecal microbiota. Consequently, this intervention resulted in a reduction in systemic inflammation caused by the high-fat diet.IMPORTANCEProbiotic supplementation affected commensal bacterial proliferation, and administering probiotics increased glycolysis and activated pyruvate metabolism in the body, which is related to propanate metabolism as a result of pyruvate metabolism activation boosting bacterial fatty acid production via dopamine and carboxylic acid specialized pathways, hence contributing to increased ATP synthesis and energy metabolism activity.

Extracorporeal Blood Treatment Using Functional Magnetic Nanoclusters Mitigates Organ Dysfunction of Sepsis in Swine.

Mitigating sepsis-induced severe organ dysfunction with magnetic nanoparticles has shown remarkable advances in extracorporeal blood treatment. Nevertheless, treating large septic animals remains challenging due to insufficient magnetic separation at rapid blood flow rates (>6 L h-1) and limited incubation time in an extracorporeal circuit. Herein, superparamagnetic nanoclusters (SPNCs) coated with red blood cell (RBC) membranes are developed, which promptly capture and magnetically separate a wide range of pathogens at high blood flow rates in a swine sepsis model. The SPNCs exhibited an ultranarrow size distribution of clustered iron oxide nanocrystals and exceptionally high saturation magnetization (≈ 90 emu g-1) close to that of bulk magnetite. It is also revealed that CD47 on the RBCs allows the RBC-SPNCs to remain at a consistent concentration in the blood by evading innate immunity. The uniform size distribution of the RBC-SPNCs greatly enhances their effectiveness in eradicating various pathogenic materials in extracorporeal blood. The use of RBC-SPNCs for extracorporeal treatment of swine infected with multidrug-resistant E. coli is validated and found that severe bacteremic sepsis-induced organ dysfunction is significantly mitigated after 12 h. The findings highlight the potential application of RBC-SPNCs for extracorporeal therapy of severe sepsis in large animal models and potentially humans.

PD-1-positive cells contribute to the diagnosis of inflammatory bowel disease and can aid in predicting response to vedolizumab.

Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD, intestinal tuberculosis, and intestinal Behcet's disease were analyzed using multiplexed immunohistochemistry. Additionally, a separate "vedolizumab (VDZ) cohort" established in ulcerative colitis patients who underwent endoscopic biopsy before VDZ administration was analyzed to predict response to VDZ. In the immunohistochemistry analysis, the cell density of T cell subsets, including PD-1 + cells, was investigated and compared between IBD and other inflammatory diseases (OID). Cell densities of PD-1 + cells (p = 0.028), PD-1 + helper T cells (p = 0.008), and PD-1 + regulatory T cells (p = 0.024) were higher in IBD compared with OID. In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1 + cells (p = 0.026), PD-1 + helper T cells (p = 0.026), and PD-1 + regulatory T cells (p = 0.041) than the no response group. PD-1 + immune cells may contribute to the diagnosis of IBD and could be used to predict response to VDZ in ulcerative colitis patients.