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BACKGROUND: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. CASE PRESENTATION: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. CONCLUSIONS: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.
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Constipation is strongly associated with the deterioration of quality of life (QOL), and patients with constipation desire clear spontaneous defecation without the feeling of incomplete evacuation, rather than improved defecation frequency. The use of common osmotic or stimulant laxatives has not been shown to lead to a satisfactory improvement of bowel movements. In addition, softening of stools by increasing their water content has been reported to increase the frequency of spontaneous defecation and improve hard stools, straining during defecation, and abdominal symptoms, such as abdominal bloating, thereby leading to improvement of QOL deterioration caused by constipation. Thus, the present study screened bacterial strains in vitro using intestinal epithelial T84 cells, aiming to identify one that activates chloride channels involved in water secretion into the intestinal tract. As a result, the conditioned medium of Bifidobacterium longum CLA8013 was found to induce ion transport. Also, this effect was suppressed by cystic fibrosis transmembrane conductance regulator (CFTR) (inh)-172, a CFTR chloride channel inhibitor. Furthermore, both live and heat-killed CLA8013 similarly induced ion transport, suggesting that bacterial cell components are responsible for the effect. In addition, the administration of heat-killed CLA8013 to loperamide-induced constipation rats resulted in an increase in fecal water content and promoted defecation. These results suggest that the active components in CLA8013 act on CFTR chloride channels in the intestinal tract, promote water secretion into the intestinal tract, and soften stools, thereby promoting bowel movements.
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PURPOSE: To evaluate the accuracy of a new intraocular lens power calculation formula using segmental refractive index-based axial length (AL). SETTING: Chukyo Eye Clinic, Nagoya, Japan. DESIGN: Retrospective observational study. METHODS: This study included patients undergoing preoperative examination for cataract surgery with the new Barrett True AL (BTAL) and Emmetropia Verifying Optical (EVO) formulas using segmental refractive index, and conventional Barrett Universal II (BU II) formula using equivalent refractive index. The predicted refractive error of each formula was compared with the postoperative subjective spherical equivalent. RESULTS: The mean prediction error (MPE) in the short AL group (≤22 mm; 44 eyes) was 0.32 ± 0.40 diopter (D) for BU II, 0.22 ± 0.37 D for BTAL, and 0.10 ± 0.37 D for EVO ( P < .0001). MPE in the long AL group (≥26 mm; 92 eyes) was 0.01 ± 0.32 D for BU II, 0.04 ± 0.32 D for BTAL, and 0.09 ± 0.32 D for EVO ( P < .0001). In patients with an AL ≥ 28 mm, BU II showed a myopic trend in 57.1% of cases, while BTAL and EVO showed a hyperopic trend in 71.4%. The MPE for patients with an AL ≥ 28 mm was -0.16 ± 0.34 D for BU II, 0.18 ± 0.33 D for BTAL, and 0.16 ± 0.32 D for EVO ( P < .0001). CONCLUSIONS: The new EVO and BTAL formulas showed higher accuracy than BU II in short eyes, whereas there was no difference in long eyes.
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Comprimento Axial do Olho , Biometria , Implante de Lente Intraocular , Lentes Intraoculares , Óptica e Fotônica , Facoemulsificação , Refração Ocular , Humanos , Estudos Retrospectivos , Biometria/métodos , Refração Ocular/fisiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Acuidade Visual/fisiologia , Idoso de 80 Anos ou maisRESUMO
Purpose: This study aimed to evaluate the efficacy of a majority decision algorithm that integrates intraoperative aberrometry (IA) and two intraocular lens (IOL) frequency formulas. The primary objective was to compare the accuracy of three formulas (IA; Sanders, Retzlaff, and Kraff/Theoretical (SRK/T); and Barrett Universal II (BUII)), in achieving emmetropia in eyes implanted with TFNT lenses (Alcon). Patients and Methods: A total of 145 eyes of 145 patients were included in the evaluation. Preoperative data were obtained from IOLMaster 700, while intraoperative data were collected from ORA SYSTEMTM. Visual acuity ≥0.8 at the 3-month post-surgery mark was confirmed. We assessed refractive prediction error (RPE), which is the difference between predicted refraction (PR) and postoperative subjective refraction. This evaluation aimed to identify the optimal IOL power with the implemented algorithm. Results: Among the 145 eyes evaluated, 55.9%, 78.7%, and 97.2% achieved postoperative subjective refraction within ±0.13 Diopters (D), ±0.25 D, and ±0.50 D, respectively. The percentages of eyes within ±0.25 D of PR varied by formula type, with values of 57%, 57%, and 54% for IA, BUII, and SRK/T, respectively. For eyes with short to medium axial length (AL<26.00 mm), the percentages within ±0.25 D of RPE were 52%, 58%, and 58% for IA, SRK/T, and BUII, respectively. In contrast, for eyes with long axial length (≥26.00 mm) the percentages were 68%, 52%, and 45% for IA, BUII, and SRK/T, respectively. Conclusion: The proposed majority decision algorithm incorporating IA and two IOL frequency formulas was effective in reducing postoperative refractive error. IA was particularly beneficial for eyes with long axial length. These findings suggest the algorithm has potential to optimize IOL power selection to improve quality of life of patients and clinical practice outcomes.
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Recent research has highlighted the importance of the gut microbiome in regulating aging, and probiotics are interventions that can promote gut health. In this study, we surveyed several novel lactic acid bacteria to examine their beneficial effect on organismal health and lifespan in C. elegans. We found that animals fed some lactic acid bacteria, including L. acidophilus 1244 and L. paracasei subsp. paracasei 2004, grew healthy. Supplementation with the lactic acid bacterial strains L. acidophilus 1244 or L. paracasei subsp. paracasei 2004 significantly improved health, including food consumption, motility, and resistance to oxidative stressor, hydrogen peroxide. Our RNA-seq analysis showed that supplementation with L. paracasei subsp. paracasei 2004 significantly increased the expression of daf-16, a C. elegans FoxO homolog, as well as genes related to the stress response. Furthermore, daf-16 deletion inhibited the longevity effect of L. paracasei subsp. paracasei 2004 supplementation. Our results suggest that L. paracasei subsp. paracasei 2004 improves health and lifespan in a DAF-16-dependent manner.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Fatores de Transcrição Forkhead , Longevidade , Probióticos , Animais , Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiologia , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Lacticaseibacillus paracasei/fisiologia , Lacticaseibacillus paracasei/genética , Estresse Oxidativo , Microbioma GastrointestinalRESUMO
Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed.
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Escherichia coli , Sulfurtransferases , Tiossulfatos , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Transporte Biológico/genética , Cristalografia por Raios X , Cisteína/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ligação Proteica , Sulfurtransferases/genética , Sulfurtransferases/metabolismo , Tiossulfatos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
The development of near-infrared (NIR) fluorophores that have both excellent chemical stability and photostability, as well as efficient cell permeability, is highly demanded. In this study, we present phospha-rhodamine (POR) dyes which display significantly improved performance for protein labeling. This is achieved by incorporating a 2-carboxy-3-benzothiophenyl group at the 9-position of the xanthene scaffold. The resulting cis and trans isomers were successfully isolated and structurally characterized using X-ray diffraction. The HaloTag ligand conjugates of the two isomers exhibited different staining abilities in live cells. While the cis isomer showed non-specific accumulation on the organelle membranes, the trans isomer selectively labeled the HaloTag-fused proteins, enabling the long-term imaging of cell division and the 5-color imaging of cell organelles. Molecular dynamics simulations of the HaloTag ligand conjugates within the lipid membrane suggested that the cis isomer is more prone to forming oligomers in the membrane. In contrast, the oligomerization of the trans isomer is effectively suppressed by its interaction with the lipid molecules. By taking advantage of the superior labeling performance of the trans isomer and its NIR-emissive properties, multi-color time-lapse super-resolution 3D imaging, namely super-resolution 5D-imaging, of the interconnected network between the endoplasmic reticulum and microtubules was achieved in living cells.
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Corantes Fluorescentes , Organelas , Rodaminas , Ligantes , Corantes Fluorescentes/química , Organelas/metabolismo , Proteínas , Microscopia de Fluorescência/métodos , LipídeosRESUMO
Mesenchymal stem cells (MSCs) have attracted a great deal of interest as a therapeutic tool for renal fibrosis. Although both adipose-derived and bone marrow-derived MSCs (ADSCs and BMSCs, respectively) suppress renal fibrosis, which of these two has a stronger therapeutic effect remains unclear. This study aimed to compare the antifibrotic effects of ADSCs and BMSCs extracted from adipose tissue and bone marrow derived from the same rats. When cultured in serum-containing medium, ADSCs had a more potent inhibitory effect than BMSCs on renal fibrosis induced by ischemia-reperfusion injury in rats. ADSCs and BMSCs cultured in serum-free medium were equally effective in suppressing renal fibrosis. Mice infused with ADSCs (serum-containing or serum-free cultivation) had a higher death rate from pulmonary embolism than those infused with BMSCs. In vitro, mRNA levels of tissue factor, tumor necrosis factor-α-induced protein 6 and prostaglandin E synthase were higher in ADSCs than in BMSCs, while that of vascular endothelial growth factor was higher in BMSCs than in ADSCs. Although ADSCs had a stronger antifibrotic effect, these findings support the consideration of thromboembolism risk in clinical applications. Our results emphasize the importance of deciding between ADSCs and BMSCs based upon the target disease and culture method.
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Células-Tronco Mesenquimais , Fator A de Crescimento do Endotélio Vascular , Ratos , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Medula Óssea , Células-Tronco Mesenquimais/metabolismo , Fibrose , Tecido Adiposo/metabolismo , Células da Medula Óssea , Diferenciação CelularRESUMO
Membrane transport proteins require a gating mechanism that opens and closes the substrate transport pathway to carry out unidirectional transport. The "gating" involves large conformational changes and is achieved via multistep reactions. However, these elementary steps have not been clarified for most transporters due to the difficulty of detecting the individual steps. Here, we propose these steps for the gate opening of the bacterial Na+ pump rhodopsin, which outwardly pumps Na+ upon illumination. We herein solved an asymmetric dimer structure of Na+ pump rhodopsin from the bacterium Indibacter alkaliphilus. In one protomer, the Arg108 sidechain is oriented toward the protein center and appears to block a Na+ release pathway to the extracellular (EC) medium. In the other protomer, however, this sidechain swings to the EC side and then opens the release pathway. Assuming that the latter protomer mimics the Na+-releasing intermediate, we examined the mechanism for the swing motion of the Arg108 sidechain. On the EC surface of the first protomer, there is a characteristic cluster consisting of Glu10, Glu159, and Arg242 residues connecting three helices. In contrast, this cluster is disrupted in the second protomer. Our experimental results suggested that this disruption is a key process. The cluster disruption induces the outward movement of the Glu159-Arg242 pair and simultaneously rotates the seventh transmembrane helix. This rotation resultantly opens a space for the swing motion of the Arg108 sidechain. Thus, cluster disruption might occur during the photoreaction and then trigger sequential conformation changes leading to the gate-open state.
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Rodopsina , Membrana Celular/metabolismo , Transporte de Íons , Íons/metabolismo , Subunidades Proteicas/metabolismo , Rodopsina/química , Rodopsina/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , AnimaisRESUMO
In the Japanese hagfish, Eptatretus burgeri, approximately 21% of the genomic DNA in germ cells (2n = 52) consists of 16 chromosomes (eliminated [E]-chromosomes) that are eliminated from presumptive somatic cells (2n = 36). To uncover the eliminated genome (E-genome), we have identified 16 eliminated repetitive DNA families from eight hagfish species, with 11 of these repeats being selectively amplified in the germline genome of E. burgeri. Furthermore, we have demonstrated that six of these sequences, namely EEEb1-6, are exclusively localized on all 16 E-chromosomes. This has led to the hypothesis that the eight pairs of E-chromosomes are derived from one pair of ancestral chromosomes via multiple duplication events over a prolonged evolutionary period. NGS analysis has recently facilitated the re-assembly of two distinct draft genomes of E. burgeri, derived from the testis and liver. This advancement allows for the prediction of not only nonrepetitive eliminated sequences but also over 100 repetitive and eliminated sequences, accomplished through K-mer-based analysis. In this study, we report four novel eliminated repetitive DNA sequences (designated as EEEb7-10) and confirm the relative chromosomal localization of all eliminated repeats (EEEb1-10) by fluorescence in situ hybridization (FISH). With the exception of EEEb10, all sequences were exclusively detected on EEEb1-positive chromosomes. Surprisingly, EEEb10 was detected as an intense signal on EEEb1-positive chromosomes and as a scattered signal on other chromosomes in germ cells. The study further divided the eight pairs of E-chromosomes into six groups based on the signal distribution of each DNA family, and fiber-FISH experiments showed that the EEEb2-10 family was dispersed in the EEEb1-positive extended chromatin fiber. These findings provide new insights into the mechanisms underlying chromosome elimination and the evolution of E-chromosomes, supporting our previous hypothesis.
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Feiticeiras (Peixe) , Animais , Masculino , Biologia Computacional , DNA , Eucromatina , Feiticeiras (Peixe)/genética , Hibridização in Situ FluorescenteRESUMO
Phacoemulsification has emerged as the global standard for cataract surgery, and various novel methods, tools, and agents have promoted surgical efficiency and reduced complications. Conventionally, the phaco tip, which cleaves and aspirates the cataractous lens, has been mainly constructed of metal. In this study, the risk of anterior capsule rupture was evaluated under conditions of different power modes, longitudinal (Mode-L), torsional (Mode-T), or both (Mode-LT), and different aspiration powers (0 or 200 mmHg), using a traditional metal phaco tip (Group-M) or a new phaco tip with a high-strength polymer overmold on the needle edge (Group-P), which was developed to reduce the risk of capsule rupture. One hundred twenty porcine eyes were used for experiments within a setting of typical human physiological intraocular pressure. We found that Group-M showed capsule rupture with a smaller ultrasound power than did Group-P, regardless of power mode or aspiration power. In Group-M, there was no significant difference in risk of capsule rupture among power modes, however in Group-P, capsule rupture was least likely to occur with Mode-T. These results provide useful information for inexperienced ophthalmologists to improve surgical safety.
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Extração de Catarata , Cristalino , Lentes , Humanos , Suínos , Animais , Olho , Cristalino/cirurgia , Extração de Catarata/efeitos adversos , Pressão IntraocularRESUMO
A placebo-controlled, randomized, double-blind study was conducted to evaluate the effect of taking 25 billion colony-forming units of heat-killed Bifidobacterium longum CLA8013 over 2 weeks on bowel movements in constipation-prone healthy individuals. The primary endpoint was the change in defecation frequency between the baseline and 2 weeks after the intake of B. longum CLA8013. The secondary endpoints were the number of days of defecation, stool volume, stool consistency, straining during defecation, pain during defecation, feeling of incomplete evacuation after defecation, abdominal bloating, fecal water content, and the Japanese version of the Patient Assessment of Constipation Quality of Life. A total of 120 individuals were assigned to two groups, 104 (control group, n=51; treatment group, n=53) of whom were included in the analysis. After 2 weeks of consuming the heat-killed B. longum CLA8013, defecation frequency increased significantly in the treatment group compared with that in the control group. Furthermore, compared with the control group, the treatment group showed a significant increase in stool volume and significant improvement in stool consistency, straining during defecation, and pain during defecation. No adverse events attributable to the heat-killed B. longum CLA8013 were observed during the study period. This study revealed that heat-killed B. longum CLA8013 improved the bowel movements of constipation-prone healthy individuals and confirmed that there were no relevant safety issues.
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BACKGROUND AND AIM: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. METHODS: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. RESULTS: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. CONCLUSION: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.
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Antineoplásicos , Microbioma Gastrointestinal , Humanos , Disbiose/induzido quimicamente , Diarreia/tratamento farmacológico , Bactérias , Antineoplásicos/uso terapêutico , RNA Ribossômico 16SRESUMO
Molybdenum carbides (MoC and Mo2C) are being reported for various applications, for example, catalysts for sustainable energies, nonlinear materials for laser applications, protective coatings for improving tribological performance, and so on. A one-step method for simultaneously fabricating molybdenum monocarbide (MoC) nanoparticles (NPs) and MoC surfaces with a laser-induced periodic surface structure (LIPSS) was developed by using pulsed laser ablation of a molybdenum (Mo) substrate in hexane. Spherical NPs with an average diameter of 61 nm were observed by scanning electron microscopy. The X-ray diffraction pattern and electron diffraction (ED) pattern results indicate that a face-centered cubic MoC was successfully synthesized for the NPs and on the laser-irradiated area. Notably, the ED pattern suggests that the observed NPs are nanosized single crystals, and a carbon shell was observed on the surface of MoC NPs. The X-ray diffraction pattern of both MoC NPs and LIPSS surface indicates the formation of FCC MoC, agreeing with the results of ED. The results of X-ray photoelectron spectroscopy also showed the bonding energy attributed to Mo-C, and the sp2-sp3 transition was confirmed on the LIPSS surface. The results of Raman spectroscopy have also supported the formation of MoC and amorphous carbon structures. This simple synthesis method for MoC may provide new possibilities for preparing Mo x C-based devices and nanomaterials, which may contribute to the development of catalytic, photonic, and tribological fields.
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This study aimed to investigate the effect of being overweight on the outcome of ablation therapy for patients with early-stage hepatocellular carcinoma (HCC). This retrospective study included 198 patients with HCC who underwent radiofrequency ablation or microwave ablation at Gunma Saiseikai Maebashi Hospital between April 2017 and December 2021. We divided the patients into two groups based on their body mass index (BMI): overweight (BMI ≥ 25 kg/m2, n = 74 (37.4%)) and non-overweight (BMI < 25 kg/m2, n = 124 (62.6%)). The technical success rates (TSRs) in the first session were 78.4% and 90.3% in overweight and non-overweight patients, respectively, with a significant difference (p = 0.03). Additional ablation therapy for residual tumors was required in 15 (20.3%) overweight and 11 (8.9%) non-overweight patients (p = 0.03), resulting in 95.9% and 99.2% TSRs at the final session, respectively, without a significant difference (p = 0.3). While local tumor progression and distant recurrence rates were not significantly different between the two groups, overall survival was better in overweight patients than in non-overweight patients (p < 0.001). Despite the potential adverse impact of being overweight on public health problems, the present findings showed the relationship between being overweight and improved survival. The negative aspects of being overweight might remain as minor technical issues in HCC patients receiving ablation therapy.
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OBJECTIVE: The objective of the study was to investigate and compare the effects of manual acupuncture (MA) and electroacupuncture (EA) on current perception thresholds (CPTs) using quantitative methods. METHODS: Twenty-nine healthy volunteers participated in this prospective crossover trial, in which three acupuncture methods were compared: control, MA, and EA. Acupuncture needles were inserted to a depth of 15 mm at LI4 and LI11 on the left side and retained for 30 min with or without electrical stimulation at a frequency of 2 Hz (EA and MA, respectively). The needles were removed and participants rested for 30 min. CPT in the left mental region was measured at 2000, 250, and 5 Hz, corresponding to the activation of Aß, Aδ, and C-fibers, respectively, at four time points: baseline, T0; 15 min after needle application, T1; immediately after needle removal, T2; and 30 min after needle removal, T3. In the control session, only a sensory test was performed (without acupuncture). RESULTS: Significant effects of time course on CPT were observed (p < 0.001). CPT values increased significantly at T1, T2, and T3, compared with those at T0, at all stimulation frequencies during MA and EA. Changes in CPT values with EA were not significantly greater than those with MA. CONCLUSIONS: Both MA and EA increased the sensory thresholds of Aß, Aδ, and C-fibers in the mental region for ⩾30 min after needle removal. Additional of electrical stimulation may not confer additional benefits over needling alone. TRIAL REGISTRATION NUMBER: UMIN000017983 (University Hospital Medical Information Network Clinical Trials Registry).
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Terapia por Acupuntura , Eletroacupuntura , Humanos , Estudos Cross-Over , Estudos Prospectivos , Pontos de Acupuntura , Terapia por Acupuntura/métodos , PercepçãoRESUMO
Background/Aims: Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms frequently occur in patients with quiescent Crohn's disease (CD). To investigate the factors underlying IBS-D-like symptoms in patients with quiescent CD, we performed a comprehensive analysis of the clinical features and intestinal environment in those patients. Methods: We performed a prospective observational study of 27 patients with quiescent CD (CD activity index [CDAI] ≤ 150; C-reactive protein ≤ 0.3 mg/dL). The presence and severity of IBS-D-like symptoms, health-related quality of life, disease-specific quality of life, and status of depression and anxiety were evaluated. The level of intestinal permeability, fecal calprotectin and organic acids and the profiles of gut microbiome were analyzed. Results: Twelve of the 27 patients with quiescent CD (44.4%) had IBS-like symptoms, and these patients showed a significantly higher CDAI, IBS severity index and anxiety score than those without. The inflammatory bowel disease questionnaire score was significantly lower in the patients with IBS-D-like symptoms. There were no significant differences in small intestinal/colonic permeability or the levels of organic acids between the patients with and without IBS-D-like symptoms. Fusicatenibacter was significantly less abundant in the patients with IBS-D-like symptoms whereas their fecal calprotectin level was significantly higher (384.8 ± 310.6 mg/kg) than in patients without (161.0 ± 251.0 mg/kg). The receiver operating characteristic curve constructed to predict IBS-D-like symptoms in patients with quiescent CD using the fecal calprotectin level (cutoff, 125 mg/kg) showed a sensitivity and specificity of 73.3% and 91.7%, respectively. Conclusion: Minimal inflammation is closely associated with the development of IBS-D-like symptoms in patients with quiescent CD.
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In this study, we developed a one-step method for fabricating hydrophobic surfaces on copper (Cu) substrates. Cuprous oxide (Cu2O) with low free energy was successfully formed after low-fluence laser direct irradiation. The formation of Cu2O enhanced the hydrophobicity of the Cu substrate surface, and the contact angle linearly increased with the proportion of Cu2O. The Cu2O fabricated by low-fluence laser treatment showed the same crystal plane orientation as the pristine Cu substrate, implying an epitaxial growth of Cu2O on a Cu substrate.
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PURPOSE: Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment. METHODS: We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing. RESULTS: Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery. CONCLUSIONS: The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention.