Electron Transfer Capability in Atomic Hydrogen Reactions for Imidazole Groups Bound to the Insulating Alkanethiolate Layer on Au(111).

The charge transfer capability associated with chemical reactions at metal-organic interfaces was studied via the atomic H addition reaction for an imidazole-terminated alkanethiolate self-assembled monolayer (Im-SAM) film on Au(111) at room temperature, using near-edge X-ray absorption fine structure spectroscopy, infrared reflection absorption spectroscopy, work function measurements, and density functional theory calculations. The imidazolium cation is a stable species in liquids; therefore, it is pertinent to determine whether the hydrogenation reactions of the imidazole groups produce imidazolium cations accompanied by electron transfer to the Au substrate, even in the absence of solvate and/or counterions on the insulating alkanethiolate layer. The experiments made it clear that the imidazolium moieties were formed during the irradiation of Im-SAM with atomic H. Theoretical model calculations also revealed that the total energies and molecular orbital levels satisfied the imidazolium cation formation associated with electron transfer. In a detailed analysis of the work function change depending on H irradiation, we confirmed that some of the imidazolium radicals became cations in Im-SAM.

Left bundle branch area pacing for atrioventricular block and mild to moderately reduced left ventricular systolic function.

INTRODUCTION: The clinical efficacy of left bundle branch area pacing (LBBAP) has not been fully elucidated in patients with atrioventricular block and mild to moderately reduced left ventricular ejection fraction (LVEF). This study evaluated the impact of LBBAP on patients with an LVEF of ≤50% and dependent on ventricular pacing. METHODS AND RESULTS: Thirty-seven patients with atrioventricular block underwent successful LBBAP. All patients had a reduced LVEF of 36%-50% and underwent pacemaker implantation. Ventricular pacing was performed using the LBBAP alone throughout the follow-up period. Clinical outcomes, including death from any cause, fatal ventricular arrhythmias, hospitalization for heart failure, and echocardiographic improvements after 1 year, were assessed. Thirty-three (89%) patients were free from the composite endpoint during a median follow-up of 36 months, whereas four patients experienced noncardiovascular deaths or hospitalization for heart failure. No fatal ventricular arrhythmias occurred. LVEF was improved using LBBAP from 42.6 ± 4.7% to 52.1 ± 9.1% (p < .001). LVEF normalization (>50%) was achieved in 64.5% of patients, while in 11 patients LVEF remained stable demonstrating no deterioration (from 42.5 ± 4.7% to 42.4 ± 6.3%). Nonischemic cardiomyopathy (odds ratio, 21.52; 95% confidence interval, 1.96-236.45) and Pre-existing bundle branch block (odds ratio, 11.79; 95% confidence interval, 1.11-125.75) were independent preoperative predictors of LVEF normalization using LBBAP. CONCLUSION: LBBAP significantly improved cardiac systolic dysfunction without causing fatal ventricular arrhythmias. Moreover, LBBAP may provide a promising alternative to biventricular pacing in patients with atrioventricular block and a reduced LVEF of 36%-50%.

Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration.

Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.

Clinical significance of direct fast scarlet staining on the diagnosis of eosinophilic colitis: A comparative study focusing on the eosinophil degranulation in colonic mucosal tissue.

This study aimed to validate the DFS (direct fast scarlet) staining in the diagnosis of EC (eosinophilic colitis). The study included 50 patients with EC and 60 with control colons. Among the 60 control samples, 39 and 21 were collected from the ascending and descending colons, respectively. We compared the median number of eosinophils and frequency of eosinophil degranulation by HE (hematoxylin and eosin) and DFS staining between the EC and control groups. In the right hemi-colon, eosinophil count by HE was useful in distinguishing between EC and control (41.5 vs. 26.0 cells/HPF, p < 0.001), but the ideal cutoff value is 27.5 cells/HPF (high-power field). However, this method is not useful in the left hemi-colon (12.5 vs. 13.0 cells/HPF, p = 0.990). The presence of degranulation by DFS allows us to distinguish between the groups even in the left hemi-colon (58% vs. 5%, p < 0.001). DFS staining also enabled a more accurate determination of degranulation than HE. According to the current standard to diagnose EC (count by HE staining ≥20 cells/HPF), mucosal sampling from left hemi-colon is problematic since the number of eosinophils could not be increased even in EC. Determination of degranulated eosinophils by DFS may potentiate the diagnostic performance even in such conditions.

Visceral Fat Associated with Worsening of Recurrent Esophageal Varices in Alcoholic/Nonalcoholic Steatohepatitis-Related Liver Cirrhosis.

BACKGROUND: Alcoholic steatohepatitis and nonalcoholic steatohepatitis-related liver cirrhosis (ASH/NASH-LC) are major causes of esophageal varices (EVs). However, the association between high visceral fat and exacerbation of EVs remains unclear. The aim of this study was to clarify the association of visceral fat and recurrence rate of EVs in ASH/NASH-LC and to identify independent predictors associated with recurrence. METHODS: We retrospectively evaluated data from 94 patients who underwent endoscopic injection sclerotherapy for EVs with ASH/NASH-LC. Using the receiver operating characteristic curve for the cut-off value of visceral fat index (VFI; 46.4 cm2/m2), we classified patients as having a high VFI (n = 53) or low VFI (n = 41). Propensity score matching was used to align for background factors, and the recurrence rate of EVs was compared between the two groups. Predictors associated with esophageal variceal recurrence were identified by multivariate analysis. The recurrence rate in patients with viral LC was also investigated. RESULTS: In the overall analysis, the recurrence rate was significantly higher in the high VFI group than in the low VFI group (P = 0.023). The recurrence rate was also higher in the high VFI group than in the low VFI group after propensity score matching, in which 19 patients were matched in each group (P = 0.048). VFI and Child-Pugh score were independently associated with recurrence. Recurrence rates were comparable between the two groups in viral LC patients. CONCLUSIONS: Worsening of variceal recurrence was observed in high visceral fat patients in ASH/NASH-LC but not in viral LC. Furthermore, high visceral fat was an independent predictor associated with variceal recurrence.

Flexible Integrated Air Pressure Sensors for Monitoring Positive and Negative Pressure Distribution.

Barometric pressure monitoring typically depends on conventional rigid microelectromechanical systems (MEMS) for single-point measurements. However, applications such as fluid dynamics require mapping barometric pressure distribution to study phenomena such as pressure variations on an aircraft wing during flight. In this study, we developed a mechanically flexible, multichannel air pressure sensor sheet using laser-induced graphene (LIG). This air pressure sensor sheet is designed to be mechanically flexible, allowing it to conform to nonplanar objects. First, the crystallinity change of LIG is studied by monitoring the bottom and top surfaces, revealing the presence of multilayered graphene and amorphous-like carbon in the formation of LIG. This explains the crystallinity change before and after the transfer process. Using LIG with optimal structures, negative and positive pressure detection is achieved, enabling its use as an air pressure sensor. Finally, as a proof-of-concept for the multichannel air pressure sensor sheet, the pressure distribution on the surface of an aircraft wing model is successfully mapped out.

Predictive filtering of sensory response via orbitofrontal top-down input.

Habituation is a crucial sensory filtering mechanism whose dysregulation can lead to a continuously intense world in disorders with sensory overload. While habituation is considered to require top-down predictive signaling to suppress irrelevant inputs, the exact brain loci storing the internal predictive model and the circuit mechanisms of sensory filtering remain unclear. We found that daily neural habituation in the primary auditory cortex (A1) was reversed by inactivation of the orbitofrontal cortex (OFC). Top-down projections from the ventrolateral OFC, but not other frontal areas, carried predictive signals that grew with daily sound experience and suppressed A1 via somatostatin-expressing inhibitory neurons. Thus, prediction signals from the OFC cancel out behaviorally irrelevant anticipated stimuli by generating their "negative images" in sensory cortices.

PEDOT:PSS Wire: A Two-Terminal Synaptic Device for Operation in Electrolyte and Saline Solutions.

Synaptic devices, which are designed to emulate the synaptic functions of neurons, have recently gained attention as key elements in the development of neuromorphic hardware. To date, most synaptic devices utilizing conductive polymer materials, particularly poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), have been designed as three-terminal devices. Nevertheless, a recent study revealed that a single PEDOT:PSS wire can function as a two-terminal synaptic device through additional polymerization, which creates asymmetry in the wire diameter between the anode and cathode. Owing to its high biocompatibility, PEDOT is considered a promising candidate for use in clinical information-processing devices. However, previous studies examined the synaptic function of PEDOT:PSS only in PSS solutions. Therefore, the performance of PEDOT:PSS wires in other solutions, such as physiological saline solutions, remains unknown. Herein, we investigated the effects of operating environmental conditions (including phosphate-buffered saline (PBS)) on the synaptic functions of the asymmetric PEDOT:PSS wire. Our results indicate that the synaptic conductance change in the PEDOT:PSS wire occurred in all investigated aqueous electrolyte solutions. Moreover, we revealed the relationship between the synaptic conductance change behavior and the molecular properties of the electrolyte ions. Furthermore, the waveform of the conductance change can be controlled by adjusting the conditions for wire asymmetrization. These results demonstrate that the PEDOT:PSS wire exhibits a synaptic conductance change, yielding a waveform suitable for machine learning, even under wet conditions (i.e., in any electrolyte solution, including PBS). Therefore, PEDOT:PSS wire is a promising material for two-terminal synaptic devices applicable in clinical studies.

Long-Term Outcomes in Patients With Relatively High His-Bundle Capture Threshold After Permanent His-Bundle Pacing　- A Multicenter Clinical Study.

Background: Outcomes in patients with relatively high His-bundle (HB) capture thresholds at implantation are unknown. This study aimed to compare changes in the HB capture threshold and prognosis between patients with a relatively high threshold and those with a low threshold. Methods and Results: Forty-nine patients who underwent permanent HB pacing (HBP) were divided into two groups: low (<1.25 V at 1.0 ms; n=35) and high (1.25-2.49 V; n=14) baseline HB capture threshold groups. The HB capture threshold was evaluated at implantation, and after 1 week, 1, 3, and 6 months, and every 6 months thereafter. HB capture threshold rise was defined as threshold rise ≥1.0 V at 1.0 ms compared with implantation measures. We compared outcomes between the groups. During a mean follow-up period of 34.6 months, the high-threshold group showed a trend toward a higher incidence of HB capture threshold of ≥2.5 V (50% vs. 14%; P=0.023), HBP abandonment (29% vs. 8.6%; P=0.091), lead revision (21% vs. 2.9%; P=0.065), and clinical events (all-cause death, heart failure hospitalization, and new-onset or progression of atrial fibrillation; 50% vs. 23%; P=0.089) than the low-threshold group. A baseline HB capture threshold of ≥1.25V was an independent predictor of clinical events. Conclusions: A relatively high HB capture threshold is associated with increased risk of HBP abandonment, lead revision, and poor clinical outcomes.

Clinical feasibility of duodenum-preserving pancreatic head resection for neuroendocrine tumors of the pancreatic head as an intermediate procedure between enucleation and pancreaticoduodenectomy.

Objective: This study was performed to demonstrate the clinical application of duodenum-preserving pancreatic head resection (DPPHR) as a surgical treatment for pancreatic neuroendocrine tumors (PNETs) in terms of both curability and maintenance of postoperative quality of life. Methods: Seven patients diagnosed with PNETs underwent DPPHR from January 2011 to December 2021 at our institution. We investigated the clinical relevance of DPPHR based on the patients' clinicopathological findings. Results: The median operative time was 492 min, and the median blood loss was 302 g. Postoperative complications were evaluated according to the Clavien-Dindo classification, and postoperative intra-abdominal bleeding was observed in one patient. Pathological examination revealed a World Health Organization classification of G1 in six patients and G2 in one patient. Microvascular invasion was observed in two patients (29%); however, no patients developed lymph node metastasis or recurrence during the follow-up period. A daughter lesion was observed near the primary tumor in one patient. All patients achieved curative resection, and no tumor specimens showed positive margins. Conclusions: DPPHR facilitates anatomical resection of the pancreatic head in patients with PNETs as well as detailed pathological evaluation of the resected specimen. Therefore, this surgical procedure is an acceptable alternative to pancreaticoduodenectomy or enucleation for patients with PNETs.

The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer.

BACKGROUND: Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5-fluorouracil (5-FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5-FU with Lut in PDACs. METHODS AND RESULTS: PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5-FU. The xenograft tumors of DPYD-overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA-seq analysis of the DPYD-overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity-MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5-FU on DPYD-overexpressing xenograft tumors and PDAC of Pdx1-Cre; LSL-KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5-FU nor Lut showed significant inhibitory effects; however, the combined administration of 5-FU and Lut exhibited a significant tumor-suppressive effect in both the xenograft tumors and KPPC models. CONCLUSION: We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5-FU resistance, in PDACs. The combination therapy of Lut and 5-FU holds the potential for enhanced efficacy against PDACs.

Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.

Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores antitumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show selective hypermethylation and silencing of the cytoplasmic double-stranded DNA (dsDNA) sensor CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase (TE-RT) activates cGAS, triggering viral mimicry and stimulating antitumor immunity. In summary, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous RT activity to the mechanism of action of a US Food and Drug Administration-approved oncology drug.

Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets.

Biliary tract cancers (BTCs) are a group of deadly malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we present the integrative analysis of 63 BTC cell lines via multi-omics clustering and genome- scale CRISPR screens, providing a platform to illuminate BTC biology and inform therapeutic development. We identify dependencies broadly enriched in BTC compared to other cancers as well as dependencies selective to the anatomic subtypes. Notably, cholangiocarcinoma cell lines are stratified into distinct lineage subtypes based on biliary or dual biliary/hepatocyte marker signatures, associated with dependency on specific lineage survival factors. Transcriptional analysis of patient specimens demonstrates the prognostic significance of these lineage subtypes. Additionally, we delineate strategies to enhance targeted therapies or to overcome resistance in cell lines with key driver gene mutations. Furthermore, clustering based on dependencies and proteomics data elucidates unexpected functional relationships, including a BTC subgroup with partial squamous differentiation. Thus, this cell line atlas reveals potential therapeutic targets in molecularly defined BTCs, unveils biologically distinct disease subtypes, and offers a vital resource for BTC research.

Hexane insoluble fraction from purple rice extract improves steatohepatitis and fibrosis via inhibition of NF-κB and JNK signaling.

Nonalcoholic fatty liver disease (NAFLD) is fatty liver mainly related to metabolic syndrome. NAFLD with inflammation and hepatocellular damage is defined as nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. We have previously reported that a hexane insoluble fraction from an anthocyanin-rich purple rice ethanolic extract (PRE-HIF) can suppress prostate carcinogenesis. However, the extract's effect on NASH has not yet been established. In the present study, we investigated the chemopreventive effect of a PRE-HIF on NASH and liver fibrosis using a connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rat NASH model. Seven-week-old male Cx32ΔTg rats were fed a control diet, a high-fat diet (HFD), or an HFD with 1% PRE-HIF and intraperitoneal administration of dimethylnitrosamine for 17 weeks. Histological findings of NASH such as fat deposition, lobular inflammation, hepatocyte ballooning injury, and bridging fibrosis were observed in the HFD group but not in the control group, and all histological parameters were significantly improved by PRE-HIF treatment. Corresponding to the histological changes, increased expression of inflammatory cytokine mRNAs (TNF-α, IL-6, IL-18, IFN-γ, IL-1ß, TGF-ß1, TIMP1, TIMP2, COL1A1), along with and activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling were observed in the HFD group, which was significantly decreased by PRE-HIF. The number and area of hepatic precancerous glutathione S-transferase placental form-positive foci tended to be decreased by PRE-HIF. These results indicate that intake of purple rice as a dietary supplement may reduce steatohepatitis, liver injury, and fibrosis in NASH by inactivation of NF-κB or JNK.

Outcomes and Recurrence Rate of Esophageal Varices after Endoscopic Treatment in Patients with Alcoholic Cirrhosis and Viral Cirrhosis.

BACKGROUND: The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC). METHODS: We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis. RESULTS: The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively). CONCLUSION: When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.

Biological hypoxia in pre-transplant human pancreatic islets induces transplant failure in diabetic mice.

Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P < 0.0001), SLC2A8 (R = 0.3531, P = 0.0009) and HK1 (R = 0.3444, P = 0.0012) had the highest correlation with transplantation outcome. A multiple regression model of 11 genes increased the correlation (R = 0.6117, P < 0.0001). We conclude that assessing pre-transplant hypoxia in human islets via gene expression analysis is a rapid, viable alternative to conventional in vivo assessments. This approach also underscores the importance of mitigating pre-transplant hypoxia in isolated islets to improve the success rate of islet transplantation.

Physiomimetic Fluidic Culture Platform on Microwell-Patterned Porous Collagen Scaffold for Human Pancreatic Islets.

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm2). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.

Protein requirements may be lower on a training compared to rest day but are not influenced by moderate training volumes in endurance trained males.

The impact of training volume on protein requirements in endurance trained males was investigated with indicator amino acid oxidation (IAAO) methodology on a recovery day (REST) or after a 10 or 20 km run while consuming a single suboptimal protein intake (0.93 g/kg/day). Phenylalanine excretion (F13CO2; inverse proxy for whole body protein synthesis) was greatest and phenylalanine net balance was lowest on REST compared to post-exercise recovery with no difference between training volumes. Single point F13CO2 was indistinguishable from past IAAO studies using multiple protein intakes. Our results suggest that protein requirements may be greatest on recovery days but are not influenced by moderate training volumes in endurance athletes.

Optimal ablation settings of TactiFlex SE laser-cut irrigated-tip catheter: comparison with ThermoCool SmartTouch SurroundFlow porous irrigated-tip catheter.

BACKGROUND: The TactiFlex SE catheter (TFSE, Abbott) with a contact force (CF) sensor and a laser-cut irrigated-tip has recently become available but lacks a lesion quality marker. This study aimed to explore distinctions in lesion characteristics between the TFSE and the ThermoCool SmartTouch SurroundFlow catheter (STSF, Biosense Webster), which utilizes a porous irrigated tip, and to assess the most effective application settings for the TFSE. METHODS: Lesions were generated using varying settings of radiofrequency power (30-50 W), CF (10-20 g), application duration (10-40 s), and catheter orientation (perpendicular or parallel) in an ex vivo porcine model. Comparative analysis between the TFSE and STSF was conducted for lesion characteristics and incidence of steam pops using predictive models in regression analyses. RESULTS: Among 720 applications, the TFSE exhibited a significantly lower incidence of steam pops compared to the STSF (0.6% vs. 36.8%, P < 0.001). Moreover, coefficients of determination (R2) for the TFSE were higher than those for the STSF concerning lesion depth (0.710 vs. 0.541) and volume (0.723 vs. 0.618). The lesion size generated with the TFSE was notably smaller than that with the STSF under identical application settings. Additionally, to achieve a lesion depth ≥ 4.0 mm, the TFSE required an application duration 8-12 s longer than the STSF under similar settings. CONCLUSIONS: The TFSE demonstrated a lower incidence of steam pops and superior predictability in lesion size compared to the STSF. However, the TFSE necessitated a longer application duration than the STSF to achieve an adequate lesion size.