The Effectiveness of Virtual Reality on Anxiety and Pain Management in Patients Undergoing Cardiac Procedures: A Systematic Review and Meta-Analysis.

Cardiac procedure-related anxiety and pain can adversely affect outcomes and lead to patient dissatisfaction. Virtual reality (VR) offers a promising alternative to traditional therapies for improving patient experience. Our objective is to synthesize evidence and assess the effectiveness of VR in reducing cardiac procedure-related anxiety and pain compared to standard of care. We conducted a comprehensive search across various online databases, including MEDLINE, EMBASE, CINAHL, Web of Sciences, and COCHRANE, to identify relevant randomized controlled trials (RCTs) focusing on VR, cardiac procedures, anxiety, and pain. We utilized a random-effect model to generate effect estimates reported as standardized mean differences (SMD) with a 95% confidence interval. Our review comprised 10 studies with a total of 621 participants (intervention arm: 301, control arm: 320). Overall, among the seven studies evaluating anxiety outcomes, no significant difference in anxiety reduction was observed between the intervention and control groups (standardized mean difference (SMD) -0.62, 95% CI -1.61, 0.37, p=0.22). However, studies using the same anxiety assessment tool demonstrated a significant improvement in the VR arm (SMD -1.01, 95% CI -1.98, -0.04, p=0.04). Conversely, the narrative synthesis of four studies examining pain revealed mixed results. Our findings suggest no significant difference in anxiety reduction between the VR and control groups. Future studies should employ standardized tools for assessing and reporting anxiety and pain to better understand the potential of VR in enhancing patient experience during cardiac procedures.

Unraveling the Diagnosis of Hypocomplementemic Urticarial Vasculitis Syndrome.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare condition characterized by immune complex-mediated urticarial lesions with histological features of leukocytoclastic vasculitis, low serum complement levels, and is frequently associated with systemic manifestations. Its pathophysiology is poorly understood. We present a patient who presented with abdominal pain and skin rash. Extensive work-up was performed including skin biopsy, and the presence of angioedema, oral ulcers, low complement level, leukocytic vasculitis, and persistent eosinophilia ultimately led to the diagnosis of HUVS. This case highlights the importance of recognizing and differentiating HUVS from other cutaneous diseases, which in turn helps to optimally manage these patients.

Green-synthesized lignin nanoparticles enhance Zea mays resilience to salt stress by improving antioxidant metabolism and mitigating ultrastructural damage.

Soil salinity poses a substantial threat to agricultural productivity, resulting in far-reaching consequences. Green-synthesized lignin nanoparticles (LNPs) have emerged as significant biopolymers which effectively promote sustainable crop production and enhance abiotic stress tolerance. However, the defensive role and underlying mechanisms of LNPs against salt stress in Zea mays remain unexplored. The present study aims to elucidate two aspects: firstly, the synthesis of lignin nanoparticles from alkali lignin, which were characterized using Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Fourier Infrared Spectroscopy (FT-IR) and Energy Dispersive X-Ray Spectroscopy (EDX). The results confirmed the purity and morphology of LNPs. Secondly, the utilization of LNPs (200 mg/L) in nano priming to alleviate the adverse effects of NaCl (150 mM) on Zea mays seedlings. LNPs significantly reduced the accumulation of Na+ (17/21%) and MDA levels (21/28%) in shoots/roots while increased lignin absorption (30/31%), resulting in improved photosynthetic performance and plant growth. Moreover, LNPs substantially improved plant biomass, antioxidant enzymatic activities and upregulated the expression of salt-tolerant genes (ZmNHX3 (1.52 & 2.81 FC), CBL (2.83 & 3.28 FC), ZmHKT1 (2.09 & 4.87 FC) and MAPK1 (3.50 & 2.39 FC) in both shoot and root tissues. Additionally, SEM and TEM observations of plant tissues confirmed the pivotal role of LNPs in mitigating NaCl-induced stress by reducing damages to guard cells, stomata and ultra-cellular structures. Overall, our findings highlight the efficacy of LNPs as a practical and cost-effective approach to alleviate NaCl-induced stress in Zea mays plants. These results offer a sustainable agri-environmental strategy for mitigating salt toxicity and enhancing crop production in saline environments.

Physicochemical properties-based hybrid machine learning technique for the prediction of SARS-CoV-2 T-cell epitopes as vaccine targets.

Majority of the existing SARS-CoV-2 vaccines work by presenting the whole pathogen in the attenuated form to immune system to invoke an immune response. On the other hand, the concept of a peptide based vaccine (PBV) is based on the identification and chemical synthesis of only immunodominant peptides known as T-cell epitopes (TCEs) to induce a specific immune response against a particular pathogen. However PBVs have received less attention despite holding huge untapped potential for boosting vaccine safety and immunogenicity. To identify these TCEs for designing PBV, wet-lab experiments are difficult, expensive, and time-consuming. Machine learning (ML) techniques can accurately predict TCEs, saving time and cost for speedy vaccine development. This work proposes novel hybrid ML techniques based on the physicochemical properties of peptides to predict SARS-CoV-2 TCEs. The proposed hybrid ML technique was evaluated using various ML model evaluation metrics and demonstrated promising results. The hybrid technique of decision tree classifier with chi-squared feature weighting technique and forward search optimal feature searching algorithm has been identified as the best model with an accuracy of 98.19%. Furthermore, K-fold cross-validation (KFCV) was performed to ensure that the model is reliable and the results indicate that the hybrid random forest model performs consistently well in terms of accuracy with respect to other hybrid approaches. The predicted TCEs are highly likely to serve as promising vaccine targets, subject to evaluations both in-vivo and in-vitro. This development could potentially save countless lives globally, prevent future epidemic-scale outbreaks, and reduce the risk of mutation escape.

Neuropathologic changes at age 90+ related to sleep duration 19 to 40 years earlier: The 90+ Study.

INTRODUCTION: We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study. METHODS: Participants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: In 264 participants, mean age at sleep self-report was 69 years, mean age at autopsy was 98 years, and mean interval between sleep self-report and autopsy was 29 years (range: 19-40). Those reporting > 8 hours of sleep had lower likelihood of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) inclusions (OR = 0.18; CI = 0.04-0.82) and amyloid beta deposits (OR = 0.34; 95% CI = 0.12-0.94). DISCUSSION: Long self-reported sleep is associated with lower odds of neurodegenerative neuropathologic changes 19 to 40 years later in the oldest-old, suggesting a potential role of sleep in accumulation of dementia-related neuropathologies. HIGHLIGHTS: Association of self-reported sleep with non-Alzheimer's disease neuropathologic changes has not been explored. Whether sleep duration is related to dementia neuropathologic changes decades later is unclear. Long self-reported sleep is associated with lower odds of Alzheimer's disease neuropathologic change 19 to 40 years later in the oldest-old. Long self-reported sleep is associated with lower odds of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change 19 to 40 years later in the oldest-old.

The Obesity Mortality Paradox in Patients with Pulmonary Embolism: Insights from a Tertiary Care Center.

Background: While obesity is associated with an increased risk of venous thromboembolism (VTE), there is some data to suggest that higher BMI is also associated with decreased all-cause mortality in patients with a pulmonary embolism (PE). Methods: Using PE Response Team (PERT) activation data from a large tertiary hospital between 27 October 2020 and 28 August 2023, we constructed a multivariate Cox proportional hazards model to assess the association between obesity as a dichotomous variable (defined as BMI ≥ 30 vs. BMI 18.5-29.9), BMI as a continuous variable, and 30-day PE-related mortality. Results: A total of 248 patients were included in this analysis (150 with obesity and 98 who were in the normal/overweight category). Obesity was associated with a lower risk of 30-day PE-related mortality (adjusted HR 0.29, p = 0.036, 95% CI 0.09-0.92). A higher BMI was paradoxically associated with a lower risk of PE-related mortality (HR = 0.91 per 1 kg/m2 increase, p = 0.049, 95% CI 0.83-0.999). Conclusions: In our contemporary cohort of patients with a PERT activation, obesity was associated with a lower risk of PE-related mortality.

Arrhythmias and Device Therapies in Cardiac Amyloidosis.

Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. The rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of the rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted, irrespective of CHA2DS2-VASc score in patients with a favorable bleeding profile; data on left appendage closure devices are still insufficient. Ventricular arrhythmias are also not uncommon, and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit.

The behavior and welfare of neglected species: some examples from fish and mammals.

Animal welfare is the state of an animal's body and mind and the level to which its requirements are satisfied. Animal welfare is affected by human decisions and actions. Numerous decisions concerning animals are driven by human desires to enhance their own lives, and some of these decisions may be influenced by self-interest or a strong emphasis on economic factors. How to assess the welfare state of animals is a central issue in animal welfare science. Two critical questions can be used to address animal welfare: first, is the animal healthy, and second, does the animal have what it needs? Both of these questions can potentially be answered using the study of animal behavior. The development of behavioral methodologies is crucial for evaluating welfare in contexts where concern for animal welfare is often highest, such as on intensive modern farms and sites where working animals are used. Herein, we discuss animal welfare by focusing on some of its major concepts and explanations. Later, to illustrate key aspects of animal welfare, we chose to examine the information that is available for some 'neglected' livestock species, which are commercially important on a global basis and found in large numbers: buffaloes (Bubalus bubalis), camels (Camelus dromedarius), donkeys (Equus asinus), mules (Equus asinus × Equus caballus), and lumpfish (Cyclopterus lumpus). We chose these species because there are major ongoing concerns about their welfare, and more research is required to help solve the various problems. Overall, there are strong imbalances in terms of the species that are usually studied in terms of animal welfare research, and we call for greater attention to those that have traditionally been neglected.

Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

Exploring Cassia mimosoïdes as a promising natural source of steroids with potent anti-cancer, urease inhibition, and antimicrobial properties.

The genus Cassia is a rich source of physiologically active secondary metabolites, including a novel compound named 21-methylene-24-ethylidene lophenol, alongside 15 known compounds. These compounds were characterized using different spectroscopic techniques. They exhibited promising antimicrobial activity, particularly against bacteria causing gastrointestinal infections. Compound 1 showed strong anti-bacterial activity against H. pylori and S. aur with MIC values of 0.28 and 0.12 µg mL-1 respectively. The study investigated their impact on H. pylori, a contributor to ulcer development, by inhibiting the urease enzyme. Inhibiting urease can reduce H. pylori's pathogenic potential, evident from the fact that the compounds evaluated toward urease enzyme showed higher inhibitory activity (1.024 ± 0.43 6.678±0.11 µM) compared to standard thiourea (IC50 = 18.61 ± 0.11 µM). Molecular docking studies confirmed their inhibitory action, with compound 7 notably outperforming thiourea in inhibiting urease (-6.95 kcal mol-1vs. -3.13 kcal mol-1). Additionally, these compounds showed positive effects on liver functioning, which H. pylori can impair. Compound 9 shows the best response against human HepG2 liver cancer cell lines i.e., % viability is 14.47% ± 0.69 and IC50 is 7.8 µM ± 0.21. These compounds hold potential as lead compounds for addressing gastrointestinal and liver disorders caused by H. pylori.

Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

Survivorship Struggles: Navigating Etiologies and Clinical Parameters of Febrile Neutropenia During Induction Chemotherapy in Acute Leukemia Patients.

Background Acute leukemia, characterized by the uncontrolled proliferation of immature white blood cell precursors, poses significant challenges during induction chemotherapy, including the elevated risk of febrile neutropenia and its associated complications. Our study aims to explain the clinical and etiological parameters of these patients in a resource-limited setting. Methods This retrospective study focused on a total of 102 adult patients with acute leukemia who developed febrile neutropenia during the induction chemotherapy phase. Patients with disease relapse, prior bone marrow transplantation, and cases of acute promyelocytic leukemia were excluded from the study. Demographical characteristics, symptoms at presentation, diagnoses, infectious causes, and outcomes were systematically reported. Infectious etiologies and detailed culture reports were meticulously tabulated, and subsequent data were analyzed. Results Of the 102 patients, 43 (42.2%) were males, with a mean age of 31.9 ± 6.5 years. During the induction chemotherapy, a total of 31 patients died of complicated febrile neutropenia. Severe vomiting was the most common symptom present in 37 (36.2%), followed by cough in 35 (34.3%) and loose stools in 28 (27.5%). Community-acquired pneumonia, neutropenic sepsis, and neutropenic colitis were among the most common etiologies of febrile neutropenia. A total of 72 (70.6%) patients had culture-proven multidrug-resistant Gram-negative bacteremia that contributed to poor outcomes. Conclusions Acute leukemia patients undergoing induction chemotherapy face high infection-associated mortality due to their immunocompromised state. Inadequate infection control measures and antimicrobial resistance contribute to the emergence of multidrug-resistant organisms. Enhanced infection prevention strategies and evidence-based antibiotic prescription guidelines are need of time in resource-limited settings such as Pakistan to address febrile neutropenia complications and bridge the existing care gap in its management.

Platinum-based targeted chemotherapies and reversal of cisplatin resistance in non-small cell lung cancer (NSCLC).

Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial.

BACKGROUND: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. METHODS: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. FINDINGS: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Global Immunization Crisis Amid the COVID-19 Pandemic: Implications for Pediatric Oncology.

Declining herd immunity and severe manifestation of vaccine preventable infections underscores the need for vaccinations campaigns to urgently vaccinate children who missed their routine immunizations.

Recurrent Aortic Thromboembolism Associated With TET2 Mutation in Chronic Myelomonocytic Leukemia.

Ten-eleven translocation 2 (TET2) plays a pivotal role in epigenetic regulation, cell differentiation, and the inflammatory response. It also mediates the transcriptional regulation for inflammatory cytokines, particularly interleukin-6. While loss-of-function mutation in TET2 has been associated with hematological malignancies, it has been increasingly recognized to cause atherosclerotic disease. The increased atherogenicity is thought to be the result of increased production of pro-inflammatory interleukin-1ß cytokines following activation of NLRP3 inflammasomes. We present a unique case of recurrent atherothrombosis in an elderly man who was diagnosed with chronic myelomonocytic leukemia in the setting of TET2 mutation.

Real-Time Detection of Circulating Thrombi in an Extracorporeal Circuit Using Doppler Ultrasound: In-Vitro Proof of Concept Study.

BACKGROUND: Thromboembolic stroke continues to be by far the most common severe adverse event in patients supported with mechanical circulatory assist devices. Feasibility of using Doppler ultrasound to detect circulating thrombi in an extracorporeal circuit was investigated. METHODS: A mock extracorporeal circulatory loop of uncoated cardiopulmonary bypass tubing and a roller pump was setup. A Doppler bubble counter was used to monitor the mean ultrasound backscatter signal (MUBS). The study involved two sets of experiments. In Scenario 1, the circuit was sequentially primed with human blood components, and the MUBS was measured. In Scenario 2, the circuit was primed with heparinized fresh porcine blood, and the MUBS was measured. Fresh blood clots (diameter <1,000 microns, 1,000-5,000 microns, >5,000 microns) were injected into the circuit followed by protamine administration. RESULTS: In Scenario 1 (n = 3), human platelets produced a baseline MUBS of 1.5 to 3.5 volts/s. Addition of packed human red blood cells increased the baseline backscatter to 17 to 21 volts/s. Addition of fresh frozen plasma did not change the baseline backscatter. In Scenario 2 (n = 5), the blood-primed circuit produced a steady baseline MUBS. Injection of the clots resulted in abrupt and transient increase (range: 3-30 volts/s) of the baseline MUBS. Protamine administration resulted in a sustained increase of MUBS followed by circuit thrombosis. CONCLUSIONS: Doppler ultrasound may be used for real-time detection of circulating solid microemboli in the extracorporeal circuit. This technology could potentially be used to design safety systems that can reduce the risk of thromboembolic stroke associated with mechanical circulatory support therapy.