ABSTRACT
The RNA-binding protein fused in sarcoma (FUS) can form pathogenic inclusions in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Over 70 mutations in Fus are linked to ALS/FTLD. In patients, all Fus mutations are heterozygous, indicating that the mutant drives disease progression despite the presence of wild-type (WT) FUS. Here, we demonstrate that ALS/FTLD-linked FUS mutations in glycine (G) strikingly drive formation of droplets that do not readily interact with WT FUS, whereas arginine (R) mutants form mixed condensates with WT FUS. Remarkably, interactions between WT and G mutants are disfavored at the earliest stages of FUS nucleation. In contrast, R mutants physically interact with the WT FUS such that WT FUS recovers the mutant defects by reducing droplet size and increasing dynamic interactions with RNA. This result suggests disparate molecular mechanisms underlying ALS/FTLD pathogenesis and differing recovery potential depending on the type of mutation.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Frontotemporal Dementia/pathology , Glycine/metabolism , Mutation , Neuroblastoma/pathology , RNA-Binding Protein FUS/chemistry , RNA-Binding Protein FUS/metabolism , RNA/metabolism , Amyotrophic Lateral Sclerosis/genetics , Frontotemporal Dementia/genetics , Glycine/chemistry , Glycine/genetics , Humans , Inclusion Bodies , Neuroblastoma/genetics , Neuroblastoma/metabolism , Protein Conformation , RNA/chemistry , RNA/genetics , RNA-Binding Protein FUS/genetics , Tumor Cells, CulturedABSTRACT
Seminal plasma contains many morphologically heterogeneous extracellular vesicles (sEVs). These are sequentially released by cells of the testis, epididymis, and accessory sex glands and involved in male and female reproductive processes. This study aimed to define in depth sEV subsets isolated by ultrafiltration and size exclusion chromatography, decode their proteomic profiles using liquid chromatography-tandem mass spectrometry, and quantify identified proteins using sequential window acquisition of all theoretical mass spectra. The sEV subsets were defined as large (L-EVs) or small (S-EVs) by their protein concentration, morphology, size distribution, and EV-specific protein markers and purity. Liquid chromatography-tandem mass spectrometry identified a total of 1034 proteins, 737 of them quantified by SWATH in S-EVs, L-EVs, and non-EVs-enriched samples (18-20 size exclusion chromatography-eluted fractions). The differential expression analysis revealed 197 differentially abundant proteins between both EV subsets, S-EVs and L-EVs, and 37 and 199 between S-EVs and L-EVs versus non-EVs-enriched samples, respectively. The gene ontology enrichment analysis of differentially abundant proteins suggested, based on the type of protein detected, that S-EVs could be mainly released through an apocrine blebbing pathway and be involved in modulating the immune environment of the female reproductive tract as well as during sperm-oocyte interaction. In contrast, L-EVs could be released by fusion of multivesicular bodies with the plasma membrane becoming involved in sperm physiological processes, such as capacitation and avoidance of oxidative stress. In conclusion, this study provides a procedure capable of isolating subsets of EVs from pig seminal plasma with a high degree of purity and shows differences in the proteomic profile between EV subsets, indicating different sources and biological functions for the sEVs.
Subject(s)
Extracellular Vesicles , Proteome , Male , Female , Animals , Swine , Proteome/metabolism , Semen/metabolism , Proteomics/methods , Extracellular Vesicles/metabolism , Mass SpectrometryABSTRACT
Plant-microbe interactions play a pivotal role in shaping host fitness, especially concerning chemical defense mechanisms. In cycads, establishing direct correlations between specific endophytic microbes and the synthesis of highly toxic defensive phytochemicals has been challenging. Our research delves into the intricate relationship between plant-microbe associations and the variation of secondary metabolite production in two closely related Zamia species that grow in distinct habitats; terrestrial and epiphytic. Employing an integrated approach, we combined microbial metabarcoding, which characterize the leaf endophytic bacterial and fungal communities, with untargeted metabolomics to test if the relative abundances of specific microbial taxa in these two Zamia species were associated with different metabolome profiles. The two species studied shared approximately 90% of the metabolites spanning diverse biosynthetic pathways: alkaloids, amino acids, carbohydrates, fatty acids, polyketides, shikimates, phenylpropanoids, and terpenoids. Co-occurrence networks revealed positive associations among metabolites from different pathways, underscoring the complexity of their interactions. Our integrated analysis demonstrated to some degree that the intraspecific variation in metabolome profiles of the two host species was associated with the abundance of bacterial orders Acidobacteriales and Frankiales, as well as the fungal endophytes belonging to the orders Chaetothyriales, Glomerellales, Heliotiales, Hypocreales, and Sordariales. We further associate individual metabolic similarity with four specific fungal endophyte members of the core microbiota, but no specific bacterial taxa associations were identified. This study represents a pioneering investigation to characterize leaf endophytes and their association with metabolomes in tropical gymnosperms, laying the groundwork for deeper inquiries into this complex domain.
ABSTRACT
This study assessed the photoactivity of amorphous and crystalline TiO2 nanotube arrays (TNA) films in gas phase CO2 reduction. The TNA photocatalysts were fabricated by titanium anodization and submitted to an annealing treatment for crystallization and/or cathodic reduction to introduce Ti3+ and oxygen vacancies into the TiO2 structure. The cathodic reduction demonstrated a significant effect on the generated photocurrent. The photoactivity of the four TNA catalysts in CO2 reduction with water vapor was evaluated under UV irradiation for 3 h, where CH4 and H2 were detected as products. The annealed sample exhibited the best performance towards methane with a production rate of 78 µmol gcat-1 h-1, followed by the amorphous film, which also exhibited an impressive formation rate of 64 µmol gcat-1 h-1. The amorphous and reduced-amorphous films exhibited outstanding photoactivity regarding H2 production (142 and 144 µmol gcat-1 h-1, respectively). The annealed catalyst also revealed a good performance for H2 production (132 µmol gcat-1 h-1) and high stability up to five reaction cycles. Molecular dynamic simulations demonstrated the changes in the band structure by introducing oxygen vacancies. The topics covered in this study contribute to the Sustainable Development Goals (SDG), involving affordable and clean energy (SDG#7) and industry, innovation, and infrastructure (SDG#9).
Subject(s)
Carbon Dioxide , Nanotubes , Methane , Nanotubes/chemistry , OxygenABSTRACT
Mesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF-ß1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF-ß1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF-ß1 in MSCs derived from CeCa tumors (CeCa-MSCs) by interacting with both receptors and that TGF-ß1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD-L1) in CeCa-MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB-505124, a selective TGF-ß1 receptor inhibitor, in CeCa-MSC cultures significantly inhibited the expression of PD-L1. Compared with CeCa-MSCs, MSCs derived from normal cervical tissue (NCx-MSCs), used as a control and induced with Ado to express PD-L1, showed a lower response to TGF-ß1 to increase PD-L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF-ß1, and the induction of PD-L1 in CeCa-MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target.
Subject(s)
Mesenchymal Stem Cells , Uterine Cervical Neoplasms , Female , Humans , B7-H1 Antigen , Adenosine/pharmacology , Transforming Growth Factor beta1 , Tumor MicroenvironmentABSTRACT
BACKGROUND: An electronic Prospective Surveillance Model (ePSM) uses patient-reported outcomes to monitor symptoms along the cancer pathway for timely identification and treatment. Randomized controlled trials show that ePSMs can effectively manage treatment-related adverse effects. However, an understanding of optimal approaches for implementing these systems into routine cancer care is limited. This study aimed to identify barriers and facilitators prior to the implementation of an ePSM to inform the selection of implementation strategies. METHODS: A qualitative study using virtual focus groups and individual interviews was conducted with cancer survivors, oncology healthcare providers, and clinic leadership across four cancer centres in Canada. The Consolidated Framework for Implementation Research (CFIR) guided the interviews and analysis of barriers and facilitators based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: We conducted 13 focus groups and nine individual interviews with 13 patient participants and 56 clinic staff. Of the 39 CFIR constructs, 18 were identified as relevant determinants to the implementation. The adaptability, relative advantage, and complexity of an ePSM emerged as key intervention-level factors that could influence implementation. Knowledge of the system was important at the individual level. Within the inner setting, major determinants were the potential fit of an ePSM with clinical workflows (compatibility) and the resources that could be dedicated to the implementation effort (readiness for implementation). In the outer setting, meeting the needs of patients and the availability of rehabilitation supports were key determinants. Engaging various stakeholders was critical at the process level. CONCLUSIONS: Improving the implementation of ePSMs in routine cancer care has the potential to facilitate early identification and management of treatment-related adverse effects, thereby improving quality of life. This study provides insight into important factors that may influence the implementation of an ePSM, which can be used to select appropriate implementation strategies to address these factors.
Subject(s)
Neoplasms , Primary Health Care , Humans , Prospective Studies , Quality of Life , Qualitative Research , ElectronicsABSTRACT
Seminal plasma contains a heterogeneous population of extracellular vesicles (sEVs) that remains poorly characterized. This study aimed to characterize the lipidomic profile of two subsets of differently sized sEVs, small (S-) and large (L-), isolated from porcine seminal plasma by size-exclusion chromatography and characterized by an orthogonal approach. High-performance liquid chromatography-high-resolution mass spectrometry was used for lipidomic analysis. A total of 157 lipid species from 14 lipid classes of 4 major categories (sphingolipids, glycerophospholipids, glycerolipids, and sterols) were identified. Qualitative differences were limited to two cholesteryl ester species present only in S-sEVs. L-sEVs had higher levels of all quantified lipid classes due to their larger membrane surface area. The distribution pattern was different, especially for sphingomyelins (more in S-sEVs) and ceramides (more in L-sEVs). In conclusion, this study reveals differences in the lipidomic profile of two subsets of porcine sEVs, suggesting that they differ in biogenesis and functionality.
Subject(s)
Extracellular Vesicles , Lipidomics , Lipids , Semen , Animals , Extracellular Vesicles/metabolism , Swine , Semen/metabolism , Semen/chemistry , Male , Lipids/analysis , Lipids/chemistry , Lipidomics/methods , Chromatography, High Pressure Liquid , Mass Spectrometry , Chromatography, GelABSTRACT
Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.
Subject(s)
Brain Neoplasms , Extracellular Vesicles , Glioblastoma , Humans , Glioblastoma/metabolism , Receptors, Calcitonin/metabolism , Cell Line, Tumor , Extracellular Vesicles/metabolism , Biomarkers, Tumor/metabolism , Carcinogenesis/metabolism , Brain Neoplasms/metabolismABSTRACT
Source and raw water quality may deteriorate due to rainfall and river flow events that occur in watersheds. The effects on raw water quality are normally detected in drinking water treatment plants (DWTPs) with a time-lag after these events in the watersheds. Early warning systems (EWSs) in DWTPs require models with high accuracy in order to anticipate changes in raw water quality parameters. Ensemble machine learning (EML) techniques have recently been used for water quality modeling to improve accuracy and decrease variance in the outcomes. We used three decision-tree-based EML models (random forest [RF], gradient boosting [GB], and eXtreme Gradient Boosting [XGB]) to predict two critical parameters for DWTPs, raw water Turbidity and UV absorbance (UV254), using rainfall and river flow time series as predictors. When modeling raw water turbidity, the three EML models (rRF-Tu2=0.87, rGB-Tu2=0.80 and rXGB-Tu2=0.81) showed very good performance metrics. For raw water UV254, the three models (rRF-UV2=0.89, rGB-UV2=0.85 and rXGB-UV2=0.88) again showed very good performance metrics. Results from this study suggest that EML approaches could be used in EWSs to anticipate changes in the quality parameters of raw water and enhance decision-making in DWTPs.
Subject(s)
Machine Learning , Water Quality , Water Purification/methods , Models, Theoretical , RiversABSTRACT
This study aimed to describe and relate the well-being perception and injury incidence of soccer players in an entire soccer season. For 37 weeks, twenty-eight male professional soccer players (25.2 ± 4.3 years old; 22.8 ± 1.4 kg/m2) daily scored (from 1: bad; to 5: perfect) well-being perception (fatigue, sleep, muscle soreness, stress and mood and Hooper Index (HI) as general status). Injuries were also registered. Results showed that players had the lowest well-being perception during Preseason (in terms of HI, fatigue, muscle soreness and stress), being lower than EarlySeason (ps < 0.05, ds > 1.0) and/or InSeason (ps < 0.05, ds > 1.0). The injury incidence was 8.3 ± 9.2/1000 h, being always higher in training compared to competition (35.0 vs 11.1/1000 h). A lower stress perception (worse) correlated with a higher rate of new injuries during PreSeason (r = -0.84), while a greater muscle soreness and fatigue correlated with the new injuries occurring in the following week during the whole season (r = -0.38 and r = -0.39, respectively). As a conclusion, the well-being perception of professional soccer players was especially low during Preseason, with fatigue, muscle soreness and stress as the most affected items that correlated with injury incidence.
ABSTRACT
Individuals with insulin resistance and obesity display higher skeletal muscle production of nonoxidized glycolytic products (i.e., lactate), and lower complete mitochondrial substrate oxidation to CO2. These findings have also been observed in individuals without obesity and are associated with an increased risk for metabolic disease. The purpose of this study was to determine if substrate preference is evident at the earliest stage of life (birth) and to provide a clinical blood marker (lactate) that could be indicative of a predisposition for metabolic disease later. We used radiolabeled tracers to assess substrate oxidation and insulin sensitivity of myogenically differentiated mesenchymal stem cells (MSCs), a proxy of infant skeletal muscle tissue, derived from umbilical cords of full-term infants. We found that greater production of nonoxidized glycolytic products (lactate, pyruvate, alanine) is directly proportional to lower substrate oxidation and insulin sensitivity in MSCs. In addition, we found an inverse relationship between the ratio of complete glucose oxidation to CO2 and infant blood lactate at 1 mo of age. Collectively, considering that higher lactate was associated with lower MSC glucose oxidation and has been shown to be implicated with metabolic disease, it may be an early indicator of infant skeletal muscle phenotype.NEW & NOTEWORTHY In infant myogenically differentiated mesenchymal stem cells, greater production of nonoxidized glycolytic products was directly proportional to lower substrate oxidation and insulin resistance. Glucose oxidation was inversely correlated with infant blood lactate. This suggests that innate differences in infant substrate oxidation exist at birth and could be associated with the development of metabolic disease later in life. Clinical assessment of infant blood lactate could be used as an early indicator of skeletal muscle phenotype.
Subject(s)
Insulin Resistance , Mesenchymal Stem Cells , Humans , Carbon Dioxide , Glycolysis/physiology , Glucose/metabolism , Muscle, Skeletal/metabolism , Obesity/metabolism , Lactic Acid/metabolism , Pyruvic Acid/metabolism , Mesenchymal Stem Cells/metabolism , Insulin/metabolismABSTRACT
Recently, a link between the biological activity of CD73 in solid tumors and multidrug resistance protein (MRP) has been proposed. Cisplatin (CP) is the most widely used anticancer agent to treat advanced and recurrent cervical cancer (CC). However, multidrug resistance protein-1 (MRP1) is overexpressed in approximately 85% of these tumors and has been strongly associated with cisplatin resistance (CPR). In this study, we examine the involvement of CD73 and the interaction of adenosine (ADO) with its receptors (ARs) in MRP1 expression in CC cells. We found that ADO positively modulates MRP1 expression in CC cells in a dose-dependent manner. The inhibition of CD73 expression with a CD73-targeted siRNA and A2AR blockade with the selective antagonist ZM241385 significantly decreased MRP1 expression and the extrusive capacity of CC cells, making them significantly more sensitive to CP treatment than cancer cells treated with MK-751, a specific MRP1 inhibitor. These results suggest CD73 inhibition or blocking ADO signaling through A2AR could be strategies to reverse CPR in patients with advanced or recurrent CC, which is characterized by very low response rates to CP (10%-20%).
Subject(s)
Uterine Cervical Neoplasms , Female , Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Cisplatin/pharmacology , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Uterine Cervical Neoplasms/drug therapyABSTRACT
3-Hydroxypropionate (3-HP) is a versatile compound for chemical synthesis and a potential building block for biodegradable polymers. Cupriavidus necator H16, a facultative chemolithoautotroph, is an attractive production chassis and has been extensively studied as a model organism for biopolymer production. Here, we engineered C. necator H16 for 3-HP biosynthesis from its central metabolism. Wild type C. necator H16 can use 3-HP as a carbon source, a highly undesirable trait for a 3-HP production chassis. However, deletion of its three (methyl-)malonate semialdehyde dehydrogenases (mmsA1, mmsA2 and mmsA3) resulted in a strain that cannot grow on 3-HP as the sole carbon source, and this strain was selected as our production host. A stepwise approach was used to construct pathways for 3-HP production via ß-alanine. Two additional gene deletion targets were identified during the pathway construction process. Deletion of the 3-hydroxypropionate dehydrogenase, encoded by hpdH, prevented the re-consumption of the 3-HP produced by our engineered strains, while deletion of gdhA1, annotated as a glutamate dehydrogenase, prevented the utilization of aspartate as a carbon source, one of the key pathway intermediates. The final strain carrying these deletions was able to produce up to 8 mM 3-HP heterotrophically. Furthermore, an engineered strain was able to produce 0.5 mM 3-HP under autotrophic conditions, using CO2 as sole carbon source. These results form the basis for establishing C. necator H16 as an efficient platform for the production of 3-HP and 3-HP-containing polymers.
Subject(s)
Cupriavidus necator , Cupriavidus necator/genetics , Cupriavidus necator/metabolism , Metabolic Engineering , Oxidoreductases/metabolism , Carbon/metabolism , Polymers/metabolismABSTRACT
Adenosine (ADO) generation in the tumor microenvironment (TME) plays important roles in the promotion of tumor growth, invasion, and metastasis and in suppression of the antitumor immune response. Recently, adenosine deaminase (ADA) activity in the TME has been proposed to be a compensatory mechanism against toxic accumulation of ADO in cancerous tissues. In the present study, the expression and functional activity of ADA in cervical cancer (CeCa) tumor cells were analyzed: C33A (HPV-), CaSki (HPV + ), and HeLa (HPV + ) cells. CeCa tumor cells, as well as activated T lymphocytes (ATLs), which were used as a positive control, showed different ADA contents in the membrane and intracellularly and a strong ability to convert ADO into inosine (INO). Treatment of tumor cells with EHNA, a specific ADA inhibitor, decreased the viability of CeCa tumor cells in a dose-dependent manner. In C33A (EHNA half maximal inhibitory concentration (IC50) = 374 µM), CaSki (EHNA IC50 = 273.6 µM), and HeLa (EHNA IC50 = 252.2 µM) cells, EHNA strongly reversed the resistance of tumor cells to the cytotoxic effect of high concentrations of ADO; 38.82 ± 3.1%, 47.18 ± 4.7%, and 71.63 ± 6.9% of the cells were apoptotic, and 40 ± 4.8%, 52 ± 5.3% and 70 ± 6.8% of the cells had mitochondrial membrane damage, respectively. In ATLs (EHNA IC50 = 391.8 µM) treated with EHNA, 32.4 ± 4.4% were apoptotic, and 32 ± 4.3% had mitochondrial membrane damage. These results suggest that the presence and activity of ADA in CeCa tumor cells can provide protection against the cytotoxic effect of high ADO contents in the TME. Therefore, the inhibition of ADA could be a strategy for the treatment of CeCa.
Subject(s)
Antineoplastic Agents , Papillomavirus Infections , Uterine Cervical Neoplasms , Adenine/pharmacology , Adenosine/metabolism , Adenosine/pharmacology , Adenosine Deaminase/metabolism , Female , Humans , Tumor Microenvironment , Uterine Cervical Neoplasms/drug therapyABSTRACT
BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.
Subject(s)
Spinal Cord Diseases , Streptococcus anginosus , Abscess/diagnosis , Humans , Magnetic Resonance Imaging , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/drug therapyABSTRACT
Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor-beta 1 (TGF-ß1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF-ß1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki-T) and in monolayers (CaSki-M). Compared with those in CaSki-M cells, CD73 expression and Ado generation ability were significantly increased in CaSki-T cells. CaSki-T cells exhibited enrichment in the CSC-like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki-M cells, CaSki-T cells produced a greater amount of TGF-ß1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class-I (MHC-I) molecules, an increase in the expression of multidrug resistance protein-I (MRP-I) and vimentin, and an increase in the protein expression levels of Snail-1 and Twist, which was strongly reversed with TGF-ß1 inhibition. These results suggest that the presence of TGF-ß1-CD73-Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.
Subject(s)
Uterine Cervical Neoplasms , 5'-Nucleotidase/metabolism , Adenosine/metabolism , Cell Line, Tumor , Female , Humans , Integrin alpha6 , Transforming Growth Factor beta1/metabolism , Transforming Growth Factors , Tumor Microenvironment , Uterine Cervical Neoplasms/pathology , VimentinABSTRACT
BACKGROUND: Acute myocardial infarction (AMI) is the rarest and least studied cardiac complication of aneurysmal subarachnoid hemorrhage (aSAH). Precise estimates of the incidence of AMI after aSAH are unavailable. Our goal was to estimate the incidence of registry-based AMI (rb-AMI) after aSAH and determine its association with clinical outcomes. METHODS: Adult patients with aSAH in the National Inpatient Samples from 2002 to 2014 were included in the study. We evaluated risk factors for rb-AMI using univariate and multivariate regression models. Clinical outcomes that were assessed included functional status at discharge, in-patient mortality, length of stay, and total hospitalization cost, adjusting for patient demographics and cardiovascular risk factors through an inverse probability weighted analysis. Subgroup analyses were further performed stratified by rb-AMI type (ST-segment elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]). RESULTS: A total of 139,734 patients with aSAH were identified, 3.6% of whom had rb-AMI. NSTEMI was the most common type of rb-AMI occurring after aSAH (71% vs. 29% for NSTEMI vs. STEMI, respectively). Patient characteristics associated with higher odds of rb-AMI included age, female sex, poor aSAH grade, and various cardiovascular risk factors. Rb-AMI was also associated with poor functional status at discharge, higher in-hospital mortality, and a longer and more costly hospital stay. CONCLUSIONS: Rb-AMI occurs in 3.6% of patients with aSAH and is associated with poor functional status at discharge, higher in-patient mortality, and a longer and more costly hospitalization. Differentiating between different types of rb-AMI would be important in optimizing the management of patients with aSAH. Our definition of rb-AMI likely includes patients with neurogenic stress cardiomyopathy, which may confound the results.
Subject(s)
Myocardial Infarction , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Subarachnoid Hemorrhage , Adult , Female , Humans , Incidence , Myocardial Infarction/epidemiology , Registries , Risk Factors , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/epidemiologyABSTRACT
Background: /Objective: Combining blood flow restriction (BFR) with endurance training is exponentially increasing although the benefits are unclear in trained athletes. We aimed to describe the effects of aerobic and/or anaerobic training programmes combined with BFR on the aerobic capacity and related sport performance of trained athletes. Methods: Databases used were MEDLINE, SPORTDiscus, LILACS, IBECS, CINHAL, COCHRANE, SCIELO and PEDro, through October 2021. For study selection, criteria included (a) clinical trials that recruited trained healthy athletes, that (b) proposed BFR in combination with aerobic/anaerobic training programmes (≥8 sessions) and that (c) evaluated either aerobic capacity or related sport performance. For data extraction, a reviewer extracted the data, and another reviewer independently verified it. The tool RoB 2 (Risk of bias 2) was used to assess risk of bias. Results: Ten studies met the eligibility criteria, capturing a total of 207 participants. Although it did not reveal any significant effects from training with BFR on aerobic capacity compared to the same training without BFR, effect sizes were extremely high. Subgroup analyses according to the intensity of the training programmes found similar results for low-to-moderate or high-intensity training compared to the same sessions without BFR. Conclusion: Although adding BFR to training sessions always produce benefits from baseline in aerobic capacity and sport performance of trained athletes, these results are not better than those observed after the same training sessions without BFR. The reduced number of studies, small sample sizes and some concerns regarding risk of bias should be highlighted as limitations. Registration number: CRD42021248212.
ABSTRACT
PURPOSE: Home-based exercise interventions offer many health benefits; however, the environments that constitute home-based exercise are not well-understood. The purpose of this study was to explore what constitutes the "home" for cancer survivors engaging in home-based exercise and identify factors of the environment that may impact exercise participation. METHODS: We conducted a qualitative exploratory study of cancer survivors receiving a home-based exercise prescription to manage their cancer-related impairments. Semi-structured interviews included photo elicitation to actively involve participants in the interview process and provide opportunities to visually "observe" environments utilized for home-based exercise. RESULTS: Sixteen participants were interviewed (n = 11 women, median age = 53.5, range = 26-74 years) and three themes emerged: (1) reasons for participating in a home-based exercise program; (2) physical environmental influences and preferences; and (3) social environmental influences and preferences. The ability to self-manage exercise and accommodate competing demands, having access to exercise facilities, feeling comfortable exercising without qualified supervision, and a desire for autonomy were reasons home-based exercise programs were preferred. Participants reported that the physical environment influenced their experience with home-based exercise and sub-themes related to a dynamic environment, indoor and outdoor characteristics, and aesthetics were identified. The social environment, with sub-themes associated with the presence of people, social climate, exercise modeling, connection, and exercise support, also related to exercise behavior. CONCLUSION: The findings highlight the influence of the physical and social environment on exercise prescription engagement. They further indicate the need for exercise professionals to consider the environment for exercise when delivering home-based exercise interventions.