Uncaria Rhynchophylla and hirsuteine as TRPV1 agonists inducing channel desensitization.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (UR) is recognized for its therapeutic applications in treating hypertension and inflammation. However, the specific molecular mechanisms how UR and its bioactive constituents modulate inflammatory pathways remain unknown. This study investigates the effects of UR extract and its constituent, hirsuteine (HST), on TRPV1 channel modulation which is related to hypertension and inflammation. MATERIALS AND METHODS: Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons. RESULTS: UR extract and HST activated TRPV1 in HEK293T cells, with repeated applications causing channel desensitization. HST application on TRPV1-positive sensory neurons significantly reduced electrical activity compared to capsaicin. CONCLUSION: This study demonstrated UR extract and HST are a novel TRPV1 agonists inducing channel desensitization and a potent agent for treatment of TRPV1 dependent pain relief.

Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation.

BACKGROUND: Meteorin-like protein (METRNL)/Interleukin-41 (IL-41) is a novel immune-secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD). METHODS: METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903-induced AD-like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single-cell RNA-seq and RNA-seq. RESULTS: METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced ß-Catenin activation, limited the expression of Th2-related molecules that attract the accumulation of Arginase-1 (Arg1)hi macrophages, dendritic cells, and activated mast cells. CONCLUSIONS: METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule ß-Catenin.

Cardiac Extracorporeal Membrane Oxygenation in Community Cardiac Surgery Program: Are the Results Comparable?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) outcomes in small centers are commonly considered less favorable than in large-volume centers. New ECMO protocols and procedures were established in our regional community hospital system as part of a cardiogenic shock initiative. This retrospective study aims to evaluate the outcomes of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) in a community hospital system with cardiac surgery capability and assess whether protocol optimization and cannulation standards result in comparable outcomes to larger centers whether the outcomes of this new ECMO program at the community hospital setting were comparable to the United States averages. METHODS: Our regional system comprises five hospitals with 1500 beds covering southwestern New Jersey, with only one of these hospitals having cardiac surgery and ECMO capability. In May 2021, the new ECMO program was initiated. Patients were screened by a multidisciplinary call, cannulated by our ECMO team, and subsequently treated by the designated team. We reviewed our cardiac ECMO outcomes over two years, from May 2021 to April 2023, in patients who required ECMO due to cardiogenic shock or as a part of extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: A total of 60 patients underwent cardiac ECMO, and all were VA ECMO, including 18 (30%) patients who required ECPR for cardiac arrest. The overall survival rate for our cardiac ECMO program turned out to be 48% (29/60), with 50% (22/42) in VA ECMO excluding ECPR and 39% (7/18) in the ECPR group. The hospital survival rate for the VA ECMO and ECPR groups was 36% (15/42) and 28% (5/18), respectively. The ELSO-reported national average for hospital survival is 48% for VA ECMO and 30% for ECPR. Considering these benchmarks, the hospital survival rate of our program did not significantly lag behind the national average. CONCLUSIONS: With protocol, cannulation standards, and ECMO management optimized, the VA ECMO results of a community hospital system with cardiac surgery capability were not inferior to those of larger centers.

Sex-Related Differences in Utilization and Outcomes of Extracorporeal Cardio-Pulmonary Resuscitation for Refractory Cardiac Arrest.

Sparse data exist on sex-related differences in extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest (rCA). We explored the role of sex on the utilization and outcomes of ECPR for rCA by retrospective analysis of the Extracorporeal Life Support Organization (ELSO) International Registry. The primary outcome was in-hospital mortality. Exploratory outcomes were discharge disposition and occurrence of any specific extracorporeal membrane oxygenation (ECMO) complications. From 1992 to 2020, a total of 7,460 adults with ECPR were identified: 30.5% women; 69.5% men; 55.9% Whites, 23.7% Asians, 8.9% Blacks, and 3.8% Hispanics. Women's age was 50.4 ± 16.9 years (mean ± standard deviation) and men's 54.7 ± 14.1 ( p < 0.001). Ischemic heart disease occurred in 14.6% women vs. 18.5% men ( p < 0.001). Overall, 28.5% survived at discharge, 30% women vs. 27.8% men ( p = 0.138). In the adjusted analysis, sex was not associated with in-hospital mortality (odds ratio [OR] = 0.93 [confidence interval {CI} = 0.80-1.08]; p = 0.374). Female sex was associated with decreased odds of neurologic, cardiovascular, and renal complications. Despite being younger and having fewer complications during ECMO, women had in-hospital mortality similar to men. Whether these findings are driven by biologic factors or disparities in health care warrants further investigation.

Anti-inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma.

Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.

Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

Racial disparities among patients on venovenous extracorporeal membrane oxygenation in the pre-Coronavirus Disease 2019 and Coronavirus Disease 2019 eras: A retrospective registry review.

Objectives: Although many studies have addressed such disparities caused by COVID-19, to our knowledge, no study has focused on the association of race on outcomes for patients with COVID-19 requiring venovenous extracorporeal membrane oxygenation support. The goal of this study was to assess association of race on death and duration on venovenous extracorporeal membrane oxygenation in both the pre-COVID-19 and COVID-19 eras. Methods: We retrospectively reviewed the Extracorporeal Life Support Organization registry and included adults (≥18 years) who required venovenous extracorporeal membrane oxygenation between January 2019 and April 2021. We performed descriptive statistics and multivariable logistic regression. Our primary outcomes were death and extracorporeal membrane oxygenation duration. Results: A total of 7477 patients were included after excluding 340 patients (4.3%) who were missing race data. In the COVID-19 era, 1474 of 2777 COVID-19-positive patients (53.1%) died. Our regression model suggested somewhat of a protective effect on death for Black and multiple race patients. Additionally, a diagnosis of COVID-19 and patients in the COVID-19 era in general, irrespective of COVID-19 diagnosis, had higher odds of death. Hispanic patients had the longest average venovenous extracorporeal membrane oxygenation run times. Conclusions: Our study using data from the international Extracorporeal Life Support Organization Registry provides updated data on patients supported with venovenous extracorporeal membrane oxygenation in the pre-COVID-19 and COVID-19 eras between 2019 and 2021 with a focus on race. Patients in the COVID-19 era group also had higher mortality compared with those in the pre-COVID-19 era even after being adjusted for COVID-19 diagnosis. Black and multiple races appeared somewhat protective in terms of death. Hispanic race was associated with longer venovenous extracorporeal membrane oxygenation duration.

Polydopamine-based plasmonic nanocomposites: rational designs and applications.

Taking advantage of its adhesive nature and chemical reactivity, polydopamine (PDA) has recently been integrated with plasmonic nanoparticles to yield unprecedented hybrid nanostructures. With advanced architectures and optical properties, PDA-based plasmonic nanocomposites have showcased their potential in a wide spectrum of plasmon-driven applications, ranging from catalysis and chemical sensing, to drug delivery and photothermal therapy. The rational design of PDA-based plasmonic nanocomposites entails different material features of PDA and necessitates a thorough understanding of the sophisticated PDA chemistry; yet, there is still a lack of a systematic review on their fabrication strategies, plasmonic properties, and applications. In this Highlight review, five representative types of PDA-based plasmonic nanocomposites will be featured. Specifically, their design principles, synthetic strategies, and optical behaviors will be elucidated with an emphasis on the irreplaceable roles of PDA in the synthetic mechanisms. Together, their essential functions in diverse applications will be outlined. Lastly, existing challenges and outlooks on the rational design and assembly of next-generation PDA-based plasmonic nanocomposites will be presented. This Highlight review aims to provide synthetic insights and hints to inspire and aid researchers to innovate PDA-based plasmonic nanocomposites.

Protocol to study immunodynamics in the tumor microenvironment using a tyramide signal amplification-based immunofluorescent multiplex panel.

Immunodynamics in the tumor microenvironment can be precisely examined by using multiple antigen identification approaches. Here, we present a protocol for capturing expression levels of multiple target proteins in the same specimen at single-cell resolution using a tyramide signal amplification-based immunofluorescent multiplexing system. We describe steps for tumor tissue microarray preparation, multiplex immunohistochemistry staining, image acquisition, and quantification. This protocol can quantify immune cells in tissues from patients or experimental disease models at a protein level. For complete details on the use and execution of this protocol, please refer to Chung et al. (2023),1 Tang et al. (2022),2 and Tang et al. (2022).3.

Comparison of assistance preferences of older adults with different functional dependence levels on domestic tasks performed by robots.

BACKGROUND: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional dependence levels are lacking. These older adults encounter varying levels of difficulty in daily living and may have distinct preferences for robot assistance. This study aimed to describe and compare the preferences for robot assistance on domestic tasks in older adults with different functional dependence levels. METHODS: This cross-sectional descriptive study recruited a convenience sample of 385 older adults in Hong Kong. They were categorized as independent, partially dependent, and dependent using the Katz Index of Independence in Activities of Daily Living. Their preferences for robot assistance on a list of 48 domestic tasks under six categories were assessed through the Assistance Preference Checklist. Differences in preferences between the three groups were compared using one-way ANOVA test. RESULTS: Findings revealed the differences and similarities in preferences between participants with different dependence levels. In most domestic tasks under the personal care category, dependent and partially dependent older adults reported a significantly lower preferences for human assistance or a higher preferences for robot assistance (p < 0.001), compared with the independent ones. The effect size varied from medium to large (eta squared = 0.07 to 0.52). However, participants, regardless of functional dependence levels, preferred human to assist in some domestic tasks under the health and leisure activities category and preferred robot to assist in most of the domestic tasks under the chores, information management, and manipulating objects category. CONCLUSIONS: Older adults with different levels of functional dependence exhibit different preferences for robotic assistance. To effectively use robots and assist older adults as they age, the specific preferences of older adults must be considered before designing and introducing robots in domestic care.

Eagle jugular syndrome presenting with intracranial hypertension - Diagnosis and illustration of pathophysiology by multi-modality imaging.

Eagle jugular syndrome is an uncommon condition caused by compression of an elongated styloid process onto the internal jugular vein. Its presentation is non-specific but may represent in severe clinical consequences including venous thrombosis and intracranial haemorrhage. Thorough understanding of local anatomy is important in understanding the pathogenesis and establishing the diagnosis. Our case reported here illustrates the use of multimodality imaging, including dynamic Computer tomography manoeuvre, in identifying the site of obstruction and guidance towards successful surgical treatment.

Enhanced neuronal activity by suffruticosol A extracted from Paeonia lactiflora via partly BDNF signaling in scopolamine-induced memory-impaired mice.

Neurodegenerative diseases are explained by progressive defects of cognitive function and memory. These defects of cognition and memory dysfunction can be induced by the loss of brain-derived neurotrophic factors (BDNF) signaling. Paeonia lactiflora is a traditionally used medicinal herb in Asian countries and some beneficial effects have been reported, including anti-oxidative, anti-inflammatory, anti-cancer activity, and potential neuroprotective effects recently. In this study, we found that suffruticosol A is a major compound in seeds of Paeonia lactiflora. When treated in a SH-SY5 cell line for measuring cell viability and cell survival, suffruticosol A increased cell viability (at 20 µM) and recovered scopolamine-induced neurodegenerative characteristics in the cells. To further confirm its neural amelioration effects in the animals, suffruticosol A (4 or 15 ng, twice a week) was administered into the third ventricle beside the brain of C57BL/6 mice for one month then the scopolamine was intraperitoneally injected into these mice to induce impairments of cognition and memory before conducting behavioral experiments. Central administration of suffruticosol A into the brain restored the memory and cognition behaviors in mice that received the scopolamine. Consistently, the central treatments of suffruticosol A showed rescued cholinergic deficits and BDNF signaling in the hippocampus of mice. Finally, we measured the long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse to figure out the restoration of the synaptic mechanism of learning and memory. Bath application of suffruticosol A (40 µM) improved LTP impairment induced by scopolamine in hippocampal slices. In conclusion, the central administration of suffruticosol A ameliorated neuronal effects partly through elevated BDNF signaling.

The central administration of vitisin a, extracted from Vitis vinifera, improves cognitive function and related signaling pathways in a scopolamine-induced dementia model.

Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by cognitive function loss and progressive memory impairment. Vitis vinifera, which is consumed in the form of fruits and wines in various countries, contains several dietary stilbenoids that have beneficial effects on neuronal disorders related to cognitive impairment. However, few studies have investigated the hypothalamic effects of vitisin A, a resveratrol tetramer derived from V. vinifera stembark, on cognitive functions and related signaling pathways. In this study, we conducted in vitro, ex vivo, and in vivo experiments with multiple biochemical and molecular analyses to investigate its pharmaceutical effects on cognitive functions. Treatment with vitisin A increased cell viability and cell survival under H2O2-exposed conditions in a neuronal SH-SY5 cell line. Ex vivo experiments showed that vitisin A treatment restored the scopolamine-induced disruption of long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse, indicating the restoration of synaptic mechanisms of learning and memory. Consistently, central administration of vitisin A ameliorated scopolamine-induced disruptions of cognitive and memory functions in C57BL/6 mice, as evidenced by Y-maze and passive avoidance tests. Further studies showed that vitisin A upregulates BDNF-CREB signaling in the hippocampus. Together, our findings suggest that vitisin A exhibits neuroprotective effects, at least partially, by upregulating BDNF-CREB signaling and LTP.

Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes.

Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1-19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 µM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 µM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation.

Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Neuromonitoring detects brain injury in patients receiving extracorporeal membrane oxygenation support.

OBJECTIVE: There is limited evidence on standardized protocols for optimal neurological monitoring methods in patients receiving extracorporeal membrane oxygenation (ECMO). We previously introduced protocolized noninvasive multimodal neuromonitoring using serial neurological examinations, electroencephalography, transcranial Doppler ultrasound, and somatosensory evoked potentials. The purpose of this study was to examine if standardized neuromonitoring is associated with detection of acute brain injury (ABI) and improved patient outcomes. METHODS: A retrospective analysis of ECMO patients who received neurocritical care consultation was performed and outcomes were reviewed. The cohort was stratified according to those who did not receive standardized neuromonitoring (era 1: 2016-2017) and those who received standardized neuromonitoring (era 2: 2017-2020). Multivariable logistic regression was used to evaluate the association between standardized neuromonitoring and ABI. RESULTS: A total of 215 patients (mean age, 54 years; 60% male) underwent ECMO (71% venoarterial-ECMO) in our institution, 70 in era 1 and 145 in era 2. The proportion of patients diagnosed with ABI were 23% in era 1 and 33% in era 2 (P = .12). In multivariable logistic regression, standardized neuromonitoring (odds ratio, 2.24; 95% CI, 1.12-4.48; P = .02) and pre-ECMO cardiac arrest (odds ratio, 2.17; 95% CI, 1.14-4.14; P = .02) were independently associated with ABI. There was a greater proportion of patients with good neurological outcomes when discharged alive in era 2 (54% vs 30%; P = .04). CONCLUSIONS: Standardized neuromonitoring was associated with increased ABIs in ECMO patients. Although neuromonitoring does not prevent ABI from occurring, it might prevent worsening with timely interventions (eg, anticoagulation management, optimizing oxygen delivery and blood pressure), leading to improved neurological outcomes at discharge.

Costs and Readmissions Associated with Type A Aortic Dissections at High- and Low-Volume Centers.

BACKGROUND: Costs and readmissions associated with type A aortic dissection repairs are not well understood. We investigated statewide readmissions, costs, and outcomes associated with the surgical management of type A aortic dissection repairs at low- and high-volume centers. METHODS: We identified all adult type A aortic dissection patients who underwent operative repair in the Maryland Health Services Cost Review Commission's database (2012-2020). Hospitals were stratified into high- (top quartile of total repairs) or low-volume centers. RESULTS: Of the 249 patients included, 193 (77.5%) were treated at a high-volume center. Patients treated at high- and low-volume centers had no differences in age, sex, race, primary payer, or severity (all p > 0.5). High- compared to low-volume centers had a greater proportion of patients transferred in (71.5% vs. 17.9%, p < 0.001). High-volume centers also had longer lengths of stay (12 vs. 8 days, p < 0.001), similar inpatient mortality (13.0% vs. 16.1%, p = 0.6), and similar proportion of patients readmitted (54.9% vs. 51.8%, p = 0.7). High-volume centers had greater index admission costs ($114,859 vs. $72,090, p < 0.001) and similar readmission costs ($48,367 vs. $42,204, p = 0.5). At high-volume centers, transferred patients compared to direct admissions had greater severity of illness (p = 0.05), similar mortality (p = 0.53), and greater lengths of stay (p = 0.05). CONCLUSIONS: High-volume centers had a greater number of patients transferred from other institutions compared to low-volume centers. High-volume centers were associated with increased index admission resource utilization, with transfer patients having higher illness severity and greater resource utilization, yet similar mortality, compared to direct admission patients.

Phytochemical investigation on the aerial parts of Veratrum versicolor f. viride Nakai and their biological activities.

Veratrum spp. have traditionally been used in folk medicine to treat various pathologies. In this study, nine compounds, comprising one simple phenolic compound (1), three stilbenoids (2-4), and five flavonoids (5-9), were isolated from the aerial parts of Veratrum versicolor f. viride Nakai. The structures of these compounds were elucidated by spectroscopic analyses and comparison with reported data. Together, all reported compounds were isolated from V. versicolor f. viride for the first time in the study. Among them, two flavone aglycone tricetins (7 and 9) have never been isolated from the genus Veratrum or the family Melanthiaceae. The ethanol extract and isolated compounds were assessed for their inhibitory effects on elastase, tyrosinase, and melanin synthesis. Compounds 5 and 7 inhibited elastase (IC50: 292.25 ± 14.39 and 800.41 ± 5.86 µM, respectively), whereas compounds 2-5 inhibited tyrosinase with IC50 values in the range of 6.42 ~ 51.19 µM, respectively. In addition, compounds 3-6 and 8 exhibited dose-dependent inhibition (70.4% ~ 91.0%) of melanogenesis at a concentration of 100 µM.

Pre-operative Machine Learning for Heart Transplant Patients Bridged with Temporary Mechanical Circulatory Support.

Background: Existing prediction models for post-transplant mortality in patients bridged to heart transplantation with temporary mechanical circulatory support (tMCS) perform poorly. A more reliable model would allow clinicians to provide better pre-operative risk assessment and develop more targeted therapies for high-risk patients. Methods: We identified adult patients in the United Network for Organ Sharing database undergoing isolated heart transplantation between 01/2009 and 12/2017 who were supported with tMCS at the time of transplant. We constructed a machine learning model using extreme gradient boosting (XGBoost) with a 70:30 train:test split to predict 1-year post-operative mortality. All pre-transplant variables available in the UNOS database were included to train the model. Shapley Additive Explanations was used to identify and interpret the most important features for XGBoost predictions. Results: A total of 1584 patients were included, with a median age of 56 (interquartile range: 46-62) and 74% male. Actual 1-year mortality was 12.1%. Out of 498 available variables, 43 were selected for the final model. The area under the receiver operator characteristics curve (AUC) for the XGBoost model was 0.71 (95% CI: 0.62-0.78). The most important variables predictive of 1-year mortality included recipient functional status, age, pulmonary capillary wedge pressure (PCWP), cardiac output, ECMO usage, and serum creatinine. Conclusions: An interpretable machine learning model trained on a large clinical database demonstrated good performance in predicting 1-year mortality for patients bridged to heart transplantation with tMCS. Machine learning may be used to enhance clinician judgement in the care of markedly high-risk transplant recipients.

Temporary Mechanical Circulatory Support for Transcatheter Aortic Valve Replacement.

INTRODUCTION: This study aimed to characterize the use of temporary mechanical circulatory support (tMCS) among patients undergoing transcatheter aortic valve replacement (TAVR) using a nationally representative database. MATERIALS AND METHODS: The 2012-2018 National Inpatient Sample was queried for adult patients who underwent isolated TAVR. The tMCS group was comprised of those who required extracorporeal membrane oxygenation, percutaneous ventricular assist device, or intra-aortic balloon pump during index hospitalization. We evaluated temporal trends in the utilization of tMCS using Cuzick's test. Furthermore, a multivariable logistic regression was used to identify factors associated with tMCS use and its impact on in-hospital mortality, selected complications, and nonhome discharge. RESULTS: Of an estimated 215,925 patients who underwent TAVR, 3085 (1.4%) required tMCS during their hospital course. The most common modality of tMCS was intra-aortic balloon pump (49%), followed by extracorporeal membrane oxygenation (27%) then percutaneous ventricular assist device (18%). Seven percent of tMCS patients were supported by > 1 device. The annual incidence of tMCS usage decreased over the study period, from 3% in 2012 to 1% in 2018 (P-trend < 0.01). Nonelective admission, congestive heart failure, coagulopathy, and liver disease were strong independent predictors of requiring tMCS. Patients requiring tMCS had a 31.8% in-hospital mortality rate (adjusted odds ratio = 23, 95% confidence interval 18.5-28.5), longer length of stay (9 d versus 3, P < 0.001), and higher costs ($84,600 versus $48,100, P < 0.001) than those who did not. CONCLUSIONS: The use of tMCS during TAVR has decreased over time but remains associated with a 23-fold increased mortality rate and significant clinical and resource utilization burden.