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OBJECTIVE: To determine the pathophysiologic and prognostic meaning of patient self-reported sodium intake in heart failure (HF) with preserved ejection fraction (HFpEF). METHODS: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial of patients enrolled in the Americas. Tertiles of baseline self-reported sodium intake were used to assess the relationship between self-reported sodium intake and clinical presentation/outcome and interactions with treatment effect of spironolactone. RESULTS: Self-reported sodium intake of 1748 patients with HFpEF included in TOPCAT were divided according to tertiles of sodium intake (47% low, 35% moderate, and 18% high sodium intake). After covariate adjustment, lower self-reported sodium intake was associated with higher risk of HF hospital admission (P=.009). Patients with lower sodium intake had higher E-wave velocity, left ventricular end diastolic volume, and estimated plasma volume (P<.001). Lower sodium intake was associated with a larger treatment effect of spironolactone on HF hospitalizations (hazard ratio, 0.69; 95% CI, 0.53 to 0.91) vs the highest tertile (hazard ratio, 1.37; 95% CI, 0.79 to 2.38; interaction P=.030). In addition, linear mixed models indicated larger reductions in blood pressure, dyspnea, and edema (all interaction P<.001) in patients with lower sodium intake receiving spironolactone. CONCLUSION: Low self-reported sodium level in HFpEF is associated with higher risk of HF hospital admissions and may indicate a sodium-vulnerable state; patients should not be falsely reassured that they are in a lower risk category despite greater adherence to medical recommendations.
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BACKGROUND: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. METHODS: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. RESULTS: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynesâ¢sâ¢cm-5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynesâ¢sâ¢cm-5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P=0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P<0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P=0.003). CONCLUSIONS: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynesâ¢sâ¢cm-5, high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.
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BACKGROUND: Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. METHODS AND RESULTS: Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre-LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post-LVAD follow-up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post-LVAD-LVEF pre-LVAD). We quantified the association of pre-LVAD HbA1c with ΔLVEF as the primary outcome, and all-cause mortality and LVAD-related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD-related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre- and post-LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre-LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end-diastolic diameter. Pre-LVAD HbA1c was not associated with all-cause mortality, but higher pre-LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD-related infection, and device thrombosis by 3 years on LVAD support (P<0.05 for all). HbA1c decreased from 6.68±1.52% pre-LVAD to 6.11±1.33% post-LVAD (P<0.001). CONCLUSIONS: Type 2 diabetes and pre-LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre-LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.
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Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Insuficiência Cardíaca , Coração Auxiliar , Função Ventricular Esquerda , Humanos , Masculino , Coração Auxiliar/efeitos adversos , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Idoso , Glicemia/metabolismo , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de TempoRESUMO
Due to continuous increase in marine plastic waste, microplastics are ubiquitous in the marine environment. However, there are few studies on the harmful effects caused by microplastics with different particle sizes, and the interaction between particle size and concentration requires further investigation. This study explored the differences in physiological and biochemical responses, photosynthesis and oxidative stress damage of the microalga Isochrysis galbana exposed to three different particle size microplastics. It was found that different particle sizes and concentrations of microplastics resulted in significant differences (p < 0.05) in the growth rate, photosynthesis, and oxidative stress level of I. galbana. With the decrease of the particle size and lowering concentration of microplastics, the growth rate, photosynthesis and oxidative stress levels of I. galbana were reduced. Significant differences in photosynthesis and oxidative stress levels were observed when I. galbana was exposed to smallest particle size and lowest concentration of microplastics. This study provides new insights about whether polystyrene microplastics of different particle sizes and concentrations exhibit complex effects on microalgae, and explores the underlying reasons for such effects. In short, this study predicts the exacerbating adverse effects of microplastic pollution on the primary productivity, with significant implications for marine food webs and ecosystem health.
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Haptófitas , Microalgas , Microplásticos , Estresse Oxidativo , Tamanho da Partícula , Poliestirenos , Poluentes Químicos da Água , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Microalgas/efeitos dos fármacos , Haptófitas/efeitos dos fármacos , Haptófitas/crescimento & desenvolvimento , Haptófitas/fisiologia , Poliestirenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacosRESUMO
Pollutants often exist as mixtures in environmental settings, creating a challenge in selecting the most effective combination of biomarkers for routine monitoring. This study was conducted seasonally in Victoria Harbour, Hong Kong, to compare the responses of nine biomarkers in the green-lipped mussel Perna viridis with respect to its tissue levels of persistent organic pollutants and heavy metals. Multivariate statistical techniques were utilised to determine the single best predictor and optimal subset of biomarkers in P. viridis for each of the four scenarios: representing overall biomarker responses in the dry season, and wet season, as well as correlating tissue levels of mixed pollutants in the dry season, and wet season. Our findings recommend lysosomal destabilisation, and the nucleic acid ratio of RNA to DNA, as the core biomarkers in P. viridis for marine pollution monitoring. The non-specificity of these biomarkers allows effective identification of pollution hotspots and guides further detailed assessment.
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Biomarcadores , Monitoramento Ambiental , Perna (Organismo) , Poluentes Químicos da Água , Animais , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Biomarcadores/análise , Hong Kong , Metais Pesados/análise , Estações do AnoRESUMO
BACKGROUND: Gait impairment is an early marker of Parkinson's disease (PD) and is frequently monitored to evaluate disease progression. Wearable sensors are increasingly being used to quantify gait in the real-world setting among people with PD (pwPD). Particularly, embedding wearables on devices or clothing that are worn daily may represent a useful strategy to improve compliance and regular monitoring of gait. RESEARCH QUESTION: The current investigation examined the validity of innovative smart glasses to measure gait among pwPD. METHODS: Participants wore the smart glasses and 6 APDM gait sensors simultaneously, while performing two walking tasks: the 3-meters Timed Up and Go test (TUG) and the 7-meters Stand and Walk (SAW) test. The following spatiotemporal gait parameters were calculated from the data collected using the two different devices: step time, step length, swing percentage, TUG duration, turn duration, and turn velocity. RESULTS: A total of 31 pwPD (mean age=68.6±8.5 years; 35.48â¯% female(N=11), mean Unified Parkinson's Disease Rating Scale (UPDRS) total score=32.1±14.7) participated in the study. Smart glasses achieved high validity in measuring step time (ICC=0.92, p=0.01) and TUG duration (ICC=0.96, p=0.03) compared to APDM sensors. On the other hand, the smart glasses did not achieve adequate validity when measuring step length, swing percentage, turn duration or turn velocity. SIGNIFICANCE: The current study suggests that smart glasses has the potential to measure TUG and step time in individuals living with PD. However, further research is needed to improve algorithms for sensors worn on the head.
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Microplastics (MPs) are pervasive environmental contaminants that have infiltrated even the most remote ecosystems. Despite their widespread distribution, the transfer patterns and impacts of MPs in remote lakes remain poorly understood. This study aimed to address the knowledge gap regarding the pathways and consequences of MP pollution in these isolated environments. Focusing on Kyêbxang Co, a remote salt lake in Tibet, this study investigated the transfer patterns, sources and ecological impacts of MPs, providing insights into their mobility and fate in pristine ecosystems. Water, sediment and biota (brine shrimp) samples from Kyêbxang Co, collected during the summer of 2020, were analyzed using µ-Raman spectroscopy to determine MP abundances, polymer types and potential sources. Findings indicated significant MP contamination in all examined media, with concentrations highlighting the role of runoff in transporting MPs to remote locations. The majority of detected MPs were small fragments (<0.5 mm), constituting over 93 %, with polypropylene being the predominant polymer type. The presence of a halocline may slow the descent of MPs, potentially increasing the exposure and ingestion risk to brine shrimp. Despite the currently low ecological risk estimated for MPs, this study underscores the need for long-term monitoring and development of a comprehensive ecological risk assessment model for MPs.
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Artemia , Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Microplásticos , Poluentes Químicos da Água , Animais , Microplásticos/análise , Microplásticos/toxicidade , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Medição de Risco , Artemia/efeitos dos fármacos , Tibet , Monitoramento Ambiental/métodosRESUMO
Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization. The pathophysiology linking HFpEF and CKD remains unclear, but it is postulated to consist of numerous bidirectional pathways, including endothelial dysfunction, inflammation, obesity, insulin resistance, and impaired sodium handling. The diagnosis of HFpEF requires certain criteria to be satisfied, including signs and symptoms consistent with volume overload caused by structural or functional cardiac abnormalities and evidence of increased cardiac filling pressures. There are numerous overlapping metabolic clinical syndromes in patients with HFpEF and CKD that can serve as targets for intervention. With an increasing number of therapies available for HFpEF and CKD as well as for obesity and diabetes, improved recognition and diagnosis are paramount for appropriate management and improved clinical outcomes in patients with both HFpEF and CKD.
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Insuficiência Cardíaca , Insuficiência Renal Crônica , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/terapia , Fatores de Risco , ComorbidadeRESUMO
INTRODUCTION: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization. METHODS: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant. RESULTS: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028. CONCLUSIONS: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support.
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Transplante de Coração , Coração Auxiliar , Isoanticorpos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Isoanticorpos/imunologia , Isoanticorpos/sangue , Seguimentos , Adulto , Fatores de Risco , Prognóstico , Estudos Retrospectivos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Rejeição de Enxerto/etiologiaRESUMO
The COVID-19 pandemic has resulted in unprecedented plastic pollution from single-used personal protective equipment (PPE), especially face masks, in coastal and marine environments. The secondary pollutants, microplastics from face masks (mask MP), rise concern about their detrimental effects on marine organisms, terrestrial organisms and even human. Using a mouse model, oral exposure to mask MP at two doses, 0.1 and 1 mg MP/day for 21 days, caused no change in animal locomotion, total weight, or sperm counts, but caused damage to sperm motility with increased curvilinear velocity (VCL). The high-dose mask MP exposure caused a significant decrease in linearity (LIN) of sperm motility. Further testicular transcriptomic analysis revealed perturbed pathways related to spermatogenesis, oxidative stress, inflammation, metabolism and energy production. Collectively, our findings substantiate that microplastics from face masks yield adverse effects on mammalian reproductive capacity, highlighting the need for improved plastic waste management and development of environmentally friendly materials.
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Máscaras , Microplásticos , Motilidade dos Espermatozoides , Animais , Masculino , Microplásticos/toxicidade , Camundongos , Motilidade dos Espermatozoides/efeitos dos fármacos , COVID-19 , Testículo/efeitos dos fármacosRESUMO
The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.
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Furosemida , Insuficiência Cardíaca , Rim , Peptídeo Natriurético Encefálico , Sódio , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Masculino , Feminino , Idoso , Projetos Piloto , Furosemida/farmacologia , Furosemida/administração & dosagem , Sódio/metabolismo , Sódio/urina , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Rim/metabolismo , Rim/fisiopatologia , Rim/efeitos dos fármacos , Pessoa de Meia-Idade , Natriurese/efeitos dos fármacos , Diuréticos/farmacologia , Diuréticos/administração & dosagem , GMP Cíclico/metabolismo , GMP Cíclico/urina , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Growing concerns regarding the reproductive toxicity associated with daily life exposure to micro-/nano-plastics (abbreviated as MNPs) have become increasingly prevalent. In reality, MNPs exposure involves a heterogeneous mixture of MNPs of different sizes rather than a single size. METHODS: In this study, an oral exposure mouse model was used to evaluate the effects of MNPs of four size ranges: 25-30â¯nm, 1-5⯵m, 20-27⯵m, and 125-150⯵m. Adult male C57BL/6â¯J mice were administered environmentally relevant concentrations of 0.1â¯mg MNPs/day for 21 days. After that, open field test and computer assisted sperm assessment (CASA) were conducted. Immunohistochemical analyses of organ and cell type localization of MNPs were evaluated. Testicular transcriptome analysis was carried out to understand the molecular mechanisms. RESULTS: Our result showed that MNPs of different size ranges all impaired sperm motility, with a decrease in progressive sperm motility, linearity and straight-line velocity of sperm movement. Alterations did not manifest in animal locomotion, body weight, or sperm count. Noteworthy effects were most pronounced in the smaller MNPs size ranges (25-30â¯nm and 1-5⯵m). Linear regression analysis substantiated a negative correlation between the size of MNPs and sperm curvilinear activity. Immunohistochemical analysis unveiled the intrusions of 1-5⯵m MNPs, but not 20-27⯵m and 125-150⯵m MNPs, into Leydig cells and testicular macrophages. Further testicular transcriptomic analysis revealed perturbations in pathways related to spermatogenesis, oxidative stress, and inflammation. Particularly within the 1-5⯵m MNPs group, a heightened perturbation in pathways linked to spermatogenesis and oxidative stress was observed. CONCLUSIONS: Our data support the size-dependent impairment of MNPs on sperm functionality, underscoring the pressing need for apprehensions about and interventions against the escalation of environmental micro-/nano-plastics contamination. This urgency is especially pertinent to small-sized MNPs.
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Camundongos Endogâmicos C57BL , Microplásticos , Tamanho da Partícula , Motilidade dos Espermatozoides , Testículo , Animais , Masculino , Motilidade dos Espermatozoides/efeitos dos fármacos , Microplásticos/toxicidade , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Camundongos , Espermatozoides/efeitos dos fármacos , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacosRESUMO
Human influence in the deep-sea is increasing as mining and drilling operations expand, and waters warm because of climate change. Here, we investigate how the long-lived deep-sea bivalve, Acesta excavata responds to sediment pollution and/or acute elevated temperatures. A. excavata were exposed to suspended sediment, acute warming, and a combination of the two treatments for 40 days. We measured O2 consumption, NH4+ release, Total Organic Carbon (TOC), and lysosomal membrane stability (LMS). We found suspended sediment and warming interacted to decrease O:N ratios, while sediment as a single stressor increased the release of TOC and warming increased NH4+ release in A. excavata. Warming also increased levels of LMS. We found A. excavata used protein catabolism to meet elevated energetic demands indicating a low tolerance to stress. A. excavata has limited capacity for physiological responses to the stressors of warming and sediment which may lead to decreased fitness of A. excavata.
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Sedimentos Geológicos , Animais , Sedimentos Geológicos/química , Mudança Climática , Bivalves/fisiologia , Estresse Fisiológico , Carbono/análiseRESUMO
AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.