Epicardial Adipose Tissue is Associated with Geometry Alteration and Diastolic Dysfunction in Prediabetic Cardiomyopathy.

BACKGROUND: Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated. PURPOSE: In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMRI). METHODS: We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMRI to determine the EAT, intramyocardial fat, and associated parameters. Multivariable logistic regression models were also used. RESULTS: In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E' (the ratio of early mitral inflow velocity to mitral annular early diastolic velocity) (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p<0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p<0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02-1.83], p=0.012; and 1.70 [0.79-3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11-1.97], p=0.032; and 2.56 [1.03-5.40], p=0.034) after adjusting for covariates. CONCLUSIONS: Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.

Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions.

AIMS: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing. METHODS AND RESULTS: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. CONCLUSION: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.

The effect of antiarrhythmic medications on the risk of cardiovascular outcomes in patients with atrial fibrillation and coronary artery disease.

BACKGROUND: While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice. METHODS: This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes. RESULTS: Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation. CONCLUSION: For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.

A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films.

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2-12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 â†’ 4→7 â†’ 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10-7 to 0.1 µM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients.

OBJECTIVE: Individuals with hyperthyroidism are at an increased risk of atrial fibrillation (AF), but the association between autoantibodies and AF or cardiovascular mortality in individuals who have returned to normal thyroid function remains unclear. METHODS: The study utilized electronic medical records from National Taiwan University Hospital between 2000 and 2022. Each hyperthyroidism patient had at least 1 thyrotropin-binding inhibiting immunoglobulin (TBII) measurement. The relationship between TBII levels and the risk of AF and cardiovascular mortality was assessed using multivariable Cox regression models and Kaplan-Meier survival analysis. RESULTS: Among the 14 618 enrolled patients over a 20-year timeframe, 173 individuals developed AF, while 46 experienced cardiovascular mortality. TBII values exceeding 35% were significantly associated with an elevated risk of AF for both the first TBII (hazard ratio {HR} 1.48 [1.05-2.08], P = .027) and mean TBII (HR 1.91 [1.37-2.65], P < .001). Furthermore, after free T4 levels had normalized, a borderline association between first TBII and AF (HR 1.59 [0.99-2.56], P = .056) was observed, while higher mean TBII increased AF (HR 1.78 [1.11-2.85], P = .017). Higher first and mean TBII burden continued to significantly impact the incidence of cardiovascular mortality (HR 6.73 [1.42-31.82], P = .016; 7.87 [1.66-37.20], P = .009). Kaplan-Meier analysis demonstrated that elevated TBII levels increased the risk of AF and cardiac mortality (log-rank P = .035 and .027, respectively). CONCLUSION: In euthyroid individuals following antithyroid treatment, elevated circulating TBII levels and burden are associated with an elevated risk of long-term incident AF and cardiovascular mortality. Further reduction of TBII level below 35% will benefit to clinical outcomes.

Left Ventricular Segmentation, Warping, and Myocardial Registration for Automated Strain Measurement.

The left ventricular global longitudinal strain (LVGLS) is a crucial prognostic indicator. However, inconsistencies in measurements due to the speckle tracking algorithm and manual adjustments have hindered its standardization and democratization. To solve this issue, we proposed a fully automated strain measurement by artificial intelligence-assisted LV segmentation contours. The LV segmentation model was trained from echocardiograms of 368 adults (11,125 frames). We compared the registration-like effects of dynamic time warping (DTW) with speckle tracking on a synthetic echocardiographic dataset in experiment-1. In experiment-2, we enrolled 80 patients to compare the DTW method with commercially available software. In experiment-3, we combined the segmentation model and DTW method to create the artificial intelligence (AI)-DTW method, which was then tested on 40 patients with general LV morphology, 20 with dilated cardiomyopathy (DCMP), and 20 with transthyretin-associated cardiac amyloidosis (ATTR-CA), 20 with severe aortic stenosis (AS), and 20 with severe mitral regurgitation (MR). Experiments-1 and -2 revealed that the DTW method is consistent with dedicated software. In experiment-3, the AI-DTW strain method showed comparable results for general LV morphology (bias - 0.137 ± 0.398%), DCMP (- 0.397 ± 0.607%), ATTR-CA (0.095 ± 0.581%), AS (0.334 ± 0.358%), and MR (0.237 ± 0.490%). Moreover, the strain curves showed a high correlation in their characteristics, with R-squared values of 0.8879-0.9452 for those LV morphology in experiment-3. Measuring LVGLS through dynamic warping of segmentation contour is a feasible method compared to traditional tracking techniques. This approach has the potential to decrease the need for manual demarcation and make LVGLS measurements more efficient and user-friendly for daily practice.

Predicting impaired cardiopulmonary exercise capacity in patients with atrial fibrillation using a simple echocardiographic marker.

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Ossicular Reconstruction With Various Degrees of Malleus Preservation in Patients With Chronic Otitis Media.

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

Sex-based differences in obstructive sleep apnea and atrial fibrillation: Implication of atrial fibrillation burden.

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p < 0.001). In the multivariate analysis, age, being a man, and BMI were significantly associated with moderate-to-severe OSA. AF burden was associated with moderate-to-severe OSA only in men (odds ratio: 1.008; 95% confidence interval: 1.001-1.014). Women and men with OSA had similar BMI (p = 0.526) and OSA severity (p = 0.754), but women were older than men (70.1 ± 1.3 vs. 63.1 ± 0.9 years, p < 0.001). Women with moderate-to-severe OSA had a lower AF burden than men did (27.6 ± 7.1 vs. 49.5 ± 3.9%, p = 0.009). Conclusions: AF burden is a sex-specific risk factor for OSA and is limited to men. In contrast, women with both AF and OSA have a lower AF burden than men, despite being older and having similar OSA severity and body habitus. Thus, AF may develop later in women with OSA than in men.

Novel scoring system derived from meta-analysis and validated in cohort population for predicting 1-year atrial fibrillation recurrence after cryoballoon catheter ablation: The HeLPS-Cryo score.

BACKGROUND: Atrial fibrillation (AF) recurrence rates in 1 year after cryoballoon ablation catheter (CBCA) are still high. We purposed to identify strong predictors for AF recurrence after the successful CBCA procedure and develop a new scoring system based only on pre-procedural parameters. METHODS: In the derivation phase, a systematic review and meta-analysis identified the strong predictors of AF recurrence after the CBCA. The pooled hazard ratio (HR) was used to create the new scoring system. The second phase validated the new scoring system in the cohort population. RESULTS: A meta-analysis including 29 cohort studies with 16196 participants confirmed that persistent AF, stroke, heart failure, and left atrial diameter (LAD) >40 mm were powerful predictors for AF recurrence after the CBCA procedure. The HeLPS-Cryo (heart failure [1], left atrial dilatation [1], persistent AF [2], and stroke [2]) was developed based on those pre-procedural predictors. It was validated in 140 patients receiving CBCA procedures and revealed excellent predictive performance for 1-year AF recurrence (AUC = 0.8877; 95% CI = 0.8208 to 0.9546). The HeLPS-Cryo score of ≥3 could predict 1-year AF recurrence with sensitivity and specificity of 78.9% and 87.9%, respectively. The positive predictive value was 66.7%, and the negative predictive value was 93.1%. CONCLUSION: The HeLPS-Cryo score can help the physician estimate the probability of 1-year AF recurrence after the successful CBCA procedure. Patients with HeLPS-Cryo score <3 are good candidates for the CBCA procedure.

A transferable in-silico augmented ischemic model for virtual myocardial perfusion imaging and myocardial infarction detection.

This paper proposes an innovative approach to generate a generalized myocardial ischemia database by modeling the virtual electrophysiology of the heart and the 12-lead electrocardiography projected by the in-silico model can serve as a ready-to-use database for automatic myocardial infarction/ischemia (MI) localization and classification. Although the virtual heart can be created by an established technique combining the cell model with personalized heart geometry to observe the spatial propagation of depolarization and repolarization waves, we developed a strategy based on the clinical pathophysiology of MI to generate a heterogeneous database with a generic heart while maintaining clinical relevance and reduced computational complexity. First, the virtual heart is simplified into 11 regions that match the types and locations, which can be diagnosed by 12-lead ECG; the major arteries were divided into 3-5 segments from the upstream to the downstream based on the general anatomy. Second, the stenosis or infarction of the major or minor coronary artery branches can cause different perfusion drops and infarct sizes. We simulated the ischemic sites in different branches of the arteries by meandering the infarction location to elaborate on possible ECG representations, which alters the infraction's size and changes the transmembrane potential (TMP) of the myocytes associated with different levels of perfusion drop. A total of 8190 different case combinations of cardiac potentials with ischemia and MI were simulated, and the corresponding ECGs were generated by forward calculations. Finally, we trained and validated our in-silico database with a sparse representation classification (SRC) and tested the transferability of the model on the real-world Physikalisch Technische Bundesanstalt (PTB) database. The overall accuracies for localizing the MI region on the PTB data achieved 0.86, which is only 2% drop compared to that derived from the simulated database (0.88). In summary, we have shown a proof-of-concept for transferring an in-silico model to real-world database to compensate for insufficient data.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

Lacticaseibacillus chiayiensis mediate intestinal microbiome and microbiota-derived metabolites regulating the growth and immunity of chicks.

Emerging evidence confirms beneficial properties of probiotics in promoting growth and immunity of farmed chicken. However, the molecular mechanisms underlying the host-microbiome interactions mediated by probiotics are not fully understood. In this study, the internal mechanisms of Lacticaseibacillus chiayiensis-mediated host-microbiome interactions and to elucidate how it promotes host growth were investigated by additional supplementation with L. chiayiensis. We conducted experiments, including intestinal cytokines, digestive enzymes test, intestinal microbiome, metabolome and transcriptome analysis. The results showed that chickens fed L. chiayiensis exhibited higher body weight gain and digestive enzyme activity, and lower pro-inflammatory cytokines, compared to controls. Microbiota sequencing analysis showed that the gut microbiota structure was reshaped with L. chiayiensis supplementation. Specifically, Lactobacillus and Escherichia increased in abundance and Enterococcus, Lactococcus, Corynebacterium, Weissella and Gallicola decreased. In addition, the bacterial community diversity was significantly increased compared to controls. Metabolomic and transcriptomic analyses revealed that higher bile acids and N-acyl amides concentrations and lower carbohydrates concentrations in L. chiayiensis-fed chickens. Meanwhile, the expression of genes related to nutrient transport and absorption in the intestine was upregulated, which reflected the enhanced digestion and absorption of nutrients in chickens supplemented with L. chiayiensis. Moreover, supplementation of L. chiayiensis down-regulated genes involved in inflammation-related, mainly involved in NF-κB signaling pathway and MHC-II mediated antigen presentation process. Cumulatively, these findings highlight that host-microbiota crosstalk enhances the host growth phenotype in two ways: by enhancing bile acid metabolism and digestive enzyme activity, and reducing the occurrence of intestinal inflammation to promote nutrient absorption and maintain intestinal health. This provides a basis for the application of LAB as an alternative to antibiotics in animal husbandry.

Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

Isolation, antibacterial characterization, and alternating tangential flow-based preparation of viable cells of Lacticaseibacillus paracasei XLK 401: Potential application in milk preservation.

It is desirable to obtain high levels of viable Lacticaseibacillus paracasei, a widely used food probiotic whose antibacterial activity and potential application in milk remain largely uninvestigated. Here, we isolated and purified the L. paracasei strain XLK 401 from food-grade blueberry ferments and found that it exhibited strong antibacterial activity against both gram-positive and gram-negative foodborne pathogens, including Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli O157, and Shigella flexneri. Then, we applied alternating tangential flow (ATF) technology to produce viable L. paracasei XLK 401 cells and its cell-free supernatant (CFS). Compared with the conventional fed-batch method, 22 h of ATF-based processing markedly increased the number of viable cells of L. paracasei XLK 401 to 12.14 ± 0.13 log cfu/mL. Additionally, the CFS exhibited good thermal stability and pH tolerance, inhibiting biofilm formation in the abovementioned foodborne pathogens. According to liquid chromatography-mass spectrometry analysis, organic acids were the main antibacterial components of XLK 401 CFS, accounting for its inhibition activity. Moreover, the CFS of L. paracasei XLK 401 effectively inhibited the growth of multidrug-resistant gram-positive Staph. aureus and gram-negative E. coli O157 pathogens in milk, and caused a reduction in the pathogenic cell counts by 6 to 7 log cfu/mL compared with untreated control, thus considerably maintaining the safety of milk samples. For the first time to our knowledge, ATF-based technology was employed to obtain viable L. paracasei on a large scale, and its CFS could serve as a broad-spectrum biopreservative for potential application against foodborne pathogens in milk products.

Right Ventricular-Vascular Uncoupling Predicts Pulmonary Hypertension in Clinically Diagnosed Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse outcomes. We aimed to determine possible echocardiographic parameters to predict the presence of PH in patients with HFpEF. METHODS AND RESULTS: A total of 113 patients with HFpEF were prospectively enrolled from November 2017 to July 2022. The patients underwent invasive cardiac catheterization and simultaneous echocardiography at rest and during exercise. The parameters indicating right ventricle-pulmonary artery uncoupling, including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and tricuspid annular systolic velocity (TAS')/PASP were calculated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH. Sixty-eight patients with HFpEF with PH and 45 without PH were included. Those with PH had lower TAPSE/PASP and TAS'/PASP at rest and during exercise compared with those without PH. Both resting/stress TAPSE/PASP and TAS'/PASP were correlated with rest/exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In multivariable regression analysis, TAPSE/PASP remained a significant predictor of exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In receiver operating characteristic curve analysis, the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH were ≤0.62 and ≤0.47, respectively. CONCLUSIONS: Right ventricle-pulmonary artery uncoupling is closely correlated with abnormal rest/exercise hemodynamics (pulmonary capillary wedge pressure and mean pulmonary artery pressure) in patients with HFpEF. TAPSE/PASP and TAS'/PASP can be useful parameters to detect PH in patients with HFpEF.

X-RIM: Extreme Recurrent Independent Mechanisms for Noise-resistant and Interpretable Stroke Risk Prediction.

Stroke is a leading cause of mortality and long-term disability worldwide. An accurate stroke risk prediction is crucial for its early detection and prevention. Using deep learning to exploit patients' time-series electronic health records (EHRs) has been shown as a promising and efficient solution for such a prediction. Although time-series data could be more informative than a single cross-section in time, real-world time-series EHRs usually have a significantly high missing rate due to irregular patient visits. This could undermine sequential data's benefits unless a proper deep-learning model design is adopted. Furthermore, deep models have long been challenged for their interpretability, which is especially crucial for medical applications. In this study, we propose an extreme design based on the concept of recurrent independent mechanisms (RIM), termed extreme RIM (X-RIM). With no need for imputation, X-RIM utilizes the information of each input feature's temporal records through independent recurrent modules. Experiments on real-world data from the National Taiwan University Hospital showed that, in terms of the area under the precision-recall curve (AUPRC), the area under the receiver-operating characteristics curve (AUROC), and Youden Index, X-RIM (AUPRC: 0.210; AUROC: 0.764; Youden: 0.373) outperformed the classic risk score CHA2DS2-VASc (AUPRC: 0.103; AUROC: 0.650; Youden: 0.223) and other benchmarks in stroke risk prediction. Additional experiments also indicate that individual feature contributions to a prediction could be evaluated intuitively under X-RIM's independent structure to enhance interpretability.