RESUMO
Molecular dynamics simulations revealed that the carbonyls of the Val residue in the conserved selectivity filter sequence TVGTG of potassium ion channels can flip away from the pore to form hydrogen bonds with the network of water molecules residing behind the selectivity filter. Such a configuration has been proposed to be relevant for C-type inactivation. Experimentally, X-ray crystallography of the KcsA channel admits the possibility that the Val carbonyls can flip, but it cannot decisively confirm the existence of such a configuration. In this study, we combined molecular dynamics simulations and line shape theory to design two-dimensional infrared spectroscopy experiments that can corroborate the existence of the selectivity filter configuration with flipped Val carbonyls. This ability to distinguish between flipped and unflipped carbonyls is based on the varying strength of the electric field inside and outside the pore, which is directly linked to carbonyl stretching frequencies that can be resolved using infrared spectroscopy.
RESUMO
This case report describes a female patient in her early 40s with left-sided cervical lymphadenopathy, facial swelling, nasal congestion, and a left nasal mass.
RESUMO
Background: Heart failure with preserved ejection fraction (HFpEF) is the predominant form of HF in older adults. It represents a heterogenous clinical syndrome that is less well understood across different ethnicities. Objectives: This study aimed to compare the clinical presentation and assess the diagnostic performance of existing HFpEF diagnostic tools between ethnic groups. Methods: A validated Natural Language Processing (NLP) algorithm was applied to the electronic health records of a large London hospital to identify patients meeting the European Society of Cardiology criteria for a diagnosis of HFpEF. NLP extracted patient demographics (including self-reported ethnicity and socioeconomic status), comorbidities, investigation results (N-terminal pro-B-type natriuretic peptide, H2FPEF scores, and echocardiogram reports), and mortality. Analyses were stratified by ethnicity and adjusted for socioeconomic status. Results: Our cohort consisted of 1,261 (64%) White, 578 (29%) Black, and 134 (7%) Asian patients meeting the European Society of Cardiology HFpEF diagnostic criteria. Compared to White patients, Black patients were younger at diagnosis and more likely to have metabolic comorbidities (obesity, diabetes, and hypertension) but less likely to have atrial fibrillation (30% vs 13%; P < 0.001). Black patients had lower N-terminal pro-B-type natriuretic peptide levels and a lower frequency of H2FPEF scores ≥6, indicative of likely HFpEF (26% vs 44%; P < 0.0001). Conclusions: Leveraging an NLP-based artificial intelligence approach to quantify health inequities in HFpEF diagnosis, we discovered that established markers systematically underdiagnose HFpEF in Black patients, possibly due to differences in the underlying comorbidity patterns. Clinicians should be aware of these limitations and its implications for treatment and trial recruitment.
RESUMO
The health and economic impacts of infectious diseases such as COVID-19 affect all levels of a community from the individual to the governing bodies. However, the spread of an infectious disease is intricately linked to the behaviour of the people within a community since crowd behaviour affects individual human behaviour, while human behaviour affects infection spread, and infection spread affects human behaviour. Capturing these feedback loops of behaviour and infection is a well-known challenge in infectious disease modelling. Here, we investigate the interface of behavioural science theory and infectious disease modelling to explore behaviour and disease (BaD) transmission models. Specifically, we incorporate a visible protective behaviour into the susceptible-infectious-recovered-susceptible (SIRS) transmission model using the socio-psychological Health Belief Model to motivate behavioural uptake and abandonment. We characterize the mathematical thresholds for BaD emergence in the BaD SIRS model and the feasible steady states. We also explore, under different infectious disease scenarios, the effects of a fully protective behaviour on long-term disease prevalence in a community, and describe how BaD modelling can investigate non-pharmaceutical interventions that target-specific components of the Health Belief Model. This transdisciplinary BaD modelling approach may reduce the health and economic impacts of future epidemics.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/transmissão , COVID-19/psicologia , COVID-19/epidemiologia , Modelo de Crenças de Saúde , Comportamentos Relacionados com a SaúdeRESUMO
BACKGROUND: In the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial, percutaneous coronary intervention (PCI) did not reduce the incidence of death or hospitalization for heart failure (HHF). OBJECTIVES: This prespecified secondary analysis investigated the effect of PCI on health status measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) combined with the primary outcome in a win ratio. METHODS: Participants with severe ischemic left ventricular dysfunction were randomized to either PCI in addition to optimal medical therapy (OMT) (PCI) or OMT alone (OMT). The primary outcome was a hierarchical composite of all-cause death, HHF, and KCCQ-Overall Summary Score (OSS) at 24 months analyzed using the unmatched win ratio. The key secondary endpoint was a KCCQ-OSS responder analysis. RESULTS: A total of 347 participants were randomized to PCI and 353 to OMT. Median age was 70.0 years (Q1-Q3: 63.3-76.1 years). Mean left ventricular ejection fraction was 27.0 ± 6.7%. PCI did not improve the primary endpoint (win ratio for PCI vs OMT: 1.05; 95% CI: 0.88-1.26; P = 0.58). PCI resulted in more KCCQ-OSS responders than OMT at 6 months (54.1% vs 40.7%; OR: 1.96; 95% CI: 1.41-2.71; P < 0.001) and fewer deteriorators (25.2% vs 31.4%; OR: 0.69; 95% CI: 0.47-1.00; P = 0.048). PCI did not impact KCCQ-OSS responders or deteriorators at 12 or 24 months. CONCLUSIONS: PCI did not improve the hierarchical composite of death, HHF, and health status at 2 years. PCI improved KCCQ-OSS at 6 months, but this benefit was not sustained to 1- or 2-year follow-up. (Revacularization for Ischemic Ventricular Dysfunction [REVIVED-BCIS2]; NCT01920048).
RESUMO
OBJECTIVE: To examine gender differences in Australian football (AF)-related concussion presentations to EDs in regional Australia. METHODS: A prospective observational study of patients presenting to 1 of the 10 EDs in Western Victoria, Australia, with an AF-related concussion was conducted. Patients were part of a larger study investigating AF injuries over a complete AF season, including pre-season training and practice matches. Information regarding concussion injuries was extracted from patient medical records, including clinical features, concurrent injuries, mechanism and context of injury. Female and male data were compared with chi-squared and Fisher's exact tests. P < 0.05 was considered significant. RESULTS: From the original cohort of 1635 patients with AF-related injuries (242 female and 1393 male), 231 (14.1%) patients were diagnosed with concussion. Thirty-eight (15.7%) females had concussions versus 193 (13.9%) males (P > 0.05). Females over the age of 16 were more likely to be concussed than males in the same age range (females n = 26, 68.4% vs males n = 94, 48.7%; P = 0.026). Neurosurgically significant head injury was rare (one case). Similar rates of concurrent injury were found between females 15 (39.5%) and males 64 (33.2%), with neck injury the single most common in 24 (10.3%) concussions. Sixty-nine patients (29%) were admitted for observation or to await the results of scans. The majority of concussions occurred in match play (87.9%). Females were more likely injured in contested ball situations (63.2% vs 37.3%; P < 0.05). CONCLUSION: Concussion rates for community-level AF presentations to regional EDs were similar between genders. Serious head injury was rare, although hospital admission for observation was common. Concurrent injuries were common, with associated neck injury most often identified. Match play accounted for the majority of head injuries.
RESUMO
OBJECTIVE: To determine (i) the prevalence of overweight and obesity among children presenting to all EDs in a large regional Australian city and (ii) whether age, sex, socioeconomic status (SES) or hospital setting (public vs private) were associated with overweight and obesity. METHODS: This prospective observational study included children aged ≥2 and <18 years who presented to any of three EDs over an 18 month period who had their height and weight measured. Age, sex and residential postcode were collected. Weight category was determined by sex and age standardised body mass index (BMI) z-score. Weight category was assessed by sex, age, SES and hospital setting with chi-squared tests, and ordinal logistic regression with cluster sandwich error estimators. Results were reported using odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Data were collected for 3827 children, of which 11.6% were obese and 19.8% overweight. The prevalence of obesity was highest in those aged 8-14 years and in those from lower SES postcodes. The likelihood of obesity was higher in the public than the private hospitals (OR 0.66, 95% CI 0.51-0.86), whereas the likelihood of overweight was similar (OR 1.00, 95% CI 0.83-1.22). CONCLUSIONS: Almost one-third of children who presented to EDs were overweight or obese. Obesity was particularly high in those aged 8-14 years and those from lower SES postcodes. In the evolving obesity crisis, the high proportion of children presenting to EDs above a healthy weight might represent an opportunity for EDs to identify and refer children for body weight and lifestyle management.
RESUMO
INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. METHODS: An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. RESULTS: Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. CONCLUSIONS: Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.
Assuntos
Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Inquéritos e Questionários , Feminino , Masculino , Choque Cardiogênico/terapia , Choque Cardiogênico/fisiopatologia , Coração AuxiliarRESUMO
Unsedated transnasal endoscopy (TNE) is an alternative method of examining the esophageal mucosa in pediatric patients with eosinophilic esophagitis (EoE), reducing cost, time, and risk associated with frequent surveillance esophagogastroduodenoscopies (EGD). Adequacy of transnasal esophageal biopsies for the evaluation of eosinophilic esophagitis histologic scoring system (EoEHSS) has not yet been evaluated. We compared procedure times, endoscopic findings, and EoEHSS scoring for EoE patients undergoing TNE versus standard EGD. Sixty-six TNE patients and 132 EGD controls matched for age (mean age 14.0 years) and disease status (29.3% active) were included. Compared to patients undergoing standard EGD, patients undergoing TNE spent 1.94 h less in the GI suite (p < 0.0001), with comparable occurrence rates of all visual endoscopic findings and most EoEHSS components. TNE serves as a useful tool for long-term disease surveillance, and consideration should be given to its use in clinical trials for EoE.
Assuntos
Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/patologia , Masculino , Adolescente , Feminino , Criança , Endoscopia do Sistema Digestório/métodos , Biópsia/métodos , Esofagoscopia/métodos , Esôfago/patologia , Esôfago/diagnóstico por imagem , Estudos de Casos e ControlesRESUMO
Transgenic, dicamba-resistant soybean and cotton were developed to enable farmers to combat weeds that had evolved resistance to the herbicide glyphosate. The dramatic increases in dicamba use these crops facilitated have led to serious problems, including the evolution of dicamba-resistant weeds and widespread damage to susceptible crops and farming communities. Disturbingly, this pattern of dicamba use has unfolded while the total herbicide applied to soybean has nearly doubled since 2006. Without substantive changes to agricultural policy and decision making, the next 'silver-bullet' agrotechnology will likely be no more than another step on the transgene-facilitated herbicide treadmill. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Glycine max , Glifosato , Resistência a Herbicidas , Herbicidas , Plantas Daninhas , Plantas Geneticamente Modificadas , Herbicidas/farmacologia , Resistência a Herbicidas/genética , Plantas Geneticamente Modificadas/genética , Glycine max/genética , Glycine max/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/genética , Transgenes , Dicamba/farmacologia , Controle de Plantas Daninhas/métodos , Gossypium/genética , Glicina/análogos & derivados , Glicina/farmacologia , Produtos Agrícolas/genéticaRESUMO
INTRODUCTION: Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. METHODS: CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. CONCLUSIONS: To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.
Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapia , Choque Cardiogênico/etiologia , Medicina Estatal , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Winter cover crop performance metrics (i.e., vegetative biomass quantity and quality) affect ecosystem services provisions, but they vary widely due to differences in agronomic practices, soil properties, and climate. Cereal rye (Secale cereale) is the most common winter cover crop in the United States due to its winter hardiness, low seed cost, and high biomass production. We compiled data on cereal rye winter cover crop performance metrics, agronomic practices, and soil properties across the eastern half of the United States. The dataset includes a total of 5,695 cereal rye biomass observations across 208 site-years between 2001-2022 and encompasses a wide range of agronomic, soils, and climate conditions. Cereal rye biomass values had a mean of 3,428 kg ha-1, a median of 2,458 kg ha-1, and a standard deviation of 3,163 kg ha-1. The data can be used for empirical analyses, to calibrate, validate, and evaluate process-based models, and to develop decision support tools for management and policy decisions.
Assuntos
Grão Comestível , Secale , Agricultura , Ecossistema , Grão Comestível/crescimento & desenvolvimento , Estações do Ano , Secale/crescimento & desenvolvimento , Solo , Estados UnidosRESUMO
OBJECTIVE: Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first ever Meta-analysis of preoperative and postoperative PHQ-9 and GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy with the goal of identifying a specific psychometric score that could be used as an indication for surgical intervention. DATA SOURCES: A comprehensive search of the literature was performed using PubMed, Embase, PsycINFO, Web of Science, and Ovid All EBM Reviews. REVIEW METHODS: Studies met inclusion criteria if they evaluated preoperative and postoperative PHQ-9 and/or GAD-7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy. Random effects Meta-analyses were used to analyze the compiled data. RESULTS: The literature search returned 1433 articles for initial review of which 6 (1105 participants) met criteria for inclusion and Meta-analysis. Meta-analysis revealed that primary hyperparathyroidism patients had significantly higher presurgical PHQ-9 scores when compared to control groups. Additionally, patients experienced a statistically significant and sustained decrease in PHQ-9 scores following parathyroidectomy. Notably, there was a dramatic decrease in the percentage of patients with PHQ-9 scores ≥10 (considered clinically significant for depression) following parathyroidectomy. CONCLUSION: Patients with primary hyperparathyroidism experience a statistically significant and sustained improvement in PHQ-9 scores following parathyroidectomy. Additionally, symptoms of anxiety and suicidal ideation appear to decrease after parathyroidectomy. We propose that a PHQ-9 score ≥10 could potentially be used as an indication for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism.
Assuntos
Hiperparatireoidismo Primário , Paratireoidectomia , Humanos , Hiperparatireoidismo Primário/cirurgia , Psicometria , Depressão , Ansiedade/etiologiaRESUMO
Understanding water dynamics at charged interfaces is of great importance in various fields, such as catalysis, biomedical processes, and solar cell materials. In this study, we implemented molecular dynamics simulations of a system of pure water interfaced with Au electrodes, on one side of which 4-mercaptobenzonitrile (4-MBN) molecules are adsorbed. We calculated time correlation functions of various dynamic quantities, such as the hydrogen bond status of the N atom of the adsorbed 4-MBN molecules, the rotational motion of the water OH bond, hydrogen bonds between 4-MBN and water, and hydrogen bonds between water molecules in the interface region. Using the Luzar-Chandler model, we analyzed the hydrogen bond dynamics between a 4-MBN and a water molecule. The dynamic quantities we calculated can be divided into two categories: those related to the collective behavior of interfacial water molecules and the H-bond interaction between a water molecule and the CN group of 4-MBN. We found that these two categories of dynamic quantities exhibit opposite trends in response to applied potentials on the Au electrode. We anticipate that the present work will help improve our understanding of the interfacial dynamics of water in various electrolyte systems.
RESUMO
Water inside biological ion channels regulates the key properties of these proteins, such as selectivity, ion conductance, and gating. In this article, we measure the picosecond spectral diffusion of amide I vibrations of an isotope-labeled KcsA potassium channel using two-dimensional infrared (2D IR) spectroscopy. By combining waiting time (100-2000 fs) 2D IR measurements of the KcsA channel including 13C18O isotope-labeled Val76 and Gly77 residues with molecular dynamics simulations, we elucidated the site-specific dynamics of water and K+ ions inside the selectivity filter of KcsA. We observe inhomogeneous 2D line shapes with extremely slow spectral diffusion. Our simulations quantitatively reproduce the experiments and show that water is the only component with any appreciable dynamics, whereas K+ ions and the protein are essentially static on a picosecond timescale. By analyzing simulated and experimental vibrational frequencies, we find that water in the selectivity filter can be oriented to form hydrogen bonds with adjacent or nonadjacent carbonyl groups with the reorientation timescales being three times slower and comparable to that of water molecules in liquid, respectively. Water molecules can reside in the cavity sufficiently far from carbonyls and behave essentially like "free" gas-phase-like water with fast reorientation times. Remarkably, no interconversion between these configurations was observed on a picosecond timescale. These dynamics are in stark contrast with liquid water, which remains highly dynamic even in the presence of ions at high concentrations.
RESUMO
AIM: Heart failure with preserved ejection fraction (HFpEF) remains under-diagnosed in clinical practice despite accounting for nearly half of all heart failure (HF) cases. Accurate and timely diagnosis of HFpEF is crucial for proper patient management and treatment. In this study, we explored the potential of natural language processing (NLP) to improve the detection and diagnosis of HFpEF according to the European Society of Cardiology (ESC) diagnostic criteria. METHODS AND RESULTS: In a retrospective cohort study, we used an NLP pipeline applied to the electronic health record (EHR) to identify patients with a clinical diagnosis of HF between 2010 and 2022. We collected demographic, clinical, echocardiographic and outcome data from the EHR. Patients were categorized according to the left ventricular ejection fraction (LVEF). Those with LVEF ≥50% were further categorized based on whether they had a clinician-assigned diagnosis of HFpEF and if not, whether they met the ESC diagnostic criteria. Results were validated in a second, independent centre. We identified 8606 patients with HF. Of 3727 consecutive patients with HF and LVEF ≥50% on echocardiogram, only 8.3% had a clinician-assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. Patients with confirmed HFpEF were hospitalized more frequently; however the ESC criteria group had a higher 5-year mortality, despite being less comorbid and experiencing fewer acute cardiovascular events. CONCLUSIONS: This study demonstrates that patients with undiagnosed HFpEF are an at-risk group with high mortality. It is possible to use NLP methods to identify likely HFpEF patients from EHR data who would likely then benefit from expert clinical review and complement the use of diagnostic algorithms.
Assuntos
Insuficiência Cardíaca , Humanos , Volume Sistólico , Função Ventricular Esquerda , Inteligência Artificial , Estudos Retrospectivos , PrognósticoRESUMO
We report the hydrogen-bonding dynamics of water to a nitrile-functionalized and plasmonic electrode surface as a function of applied voltage. The surface-enhanced two-dimensional infrared spectra exhibit hydrogen-bonded and non-hydrogen-bonded nitrile features in similar proportions, plus cross peaks between the two. Isotopic dilution experiments show that the cross peaks arise predominantly from chemical exchange between hydrogen-bonded and non-hydrogen-bonded nitriles. The chemical exchange rate depends upon voltage, with the hydrogen bond of the water to the nitriles breaking 2 to 3 times slower (>63 vs. 25 ps) under a positive as compared to a negative potential. Spectral diffusion created by hydrogen-bond fluctuations occurs on a ~1 ps timescale and is moderately potential-dependent. Timescales from molecular dynamics simulations agree qualitatively with the experiment and show that a negative voltage causes a small net displacement of water away from the surface. These results show that the voltage applied to an electrode can alter the timescales of solvent motion at its interface, which has implications for electrochemically driven reactions.
RESUMO
Plant microbiomes are the microbial communities essential to the functioning of the phytobiome-the system that consist of plants, their environment, and their associated communities of organisms. A healthy, functional phytobiome is critical to crop health, improved yields and quality food. However, crop microbiomes are relatively under-researched, and this is associated with a fundamental need to underpin phytobiome research through the provision of a supporting infrastructure. The UK Crop Microbiome Cryobank (UKCMC) project is developing a unique, integrated and open-access resource to enable the development of solutions to improve soil and crop health. Six economically important crops (Barley, Fava Bean, Oats, Oil Seed Rape, Sugar Beet and Wheat) are targeted, and the methods as well as data outputs will underpin research activity both in the UK and internationally. This manuscript describes the approaches being taken, from characterisation, cryopreservation and analysis of the crop microbiome through to potential applications. We believe that the model research framework proposed is transferable to different crop and soil systems, acting not only as a mechanism to conserve biodiversity, but as a potential facilitator of sustainable agriculture systems.