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Human land-use intensification threatens arthropod (for example, insect and spider) biodiversity across aquatic and terrestrial ecosystems. Insects and spiders play critical roles in ecosystems by accumulating and synthesizing organic nutrients such as polyunsaturated fatty acids (PUFAs). However, links between biodiversity and nutrient content of insect and spider communities have yet to be quantified. We relate insect and spider richness to biomass and PUFA-mass from stream and terrestrial communities encompassing nine land uses. PUFA-mass and biomass relate positively to biodiversity across ecosystems. In terrestrial systems, human-dominated areas have lower biomass and PUFA-mass than more natural areas, even at equivalent levels of richness. Aquatic ecosystems have consistently higher PUFA-mass than terrestrial ecosystems. Our findings reinforce the importance of conserving biodiversity and highlight the distinctive benefits of aquatic biodiversity.
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Biodiversidade , Conservação dos Recursos Naturais , Ácidos Graxos Insaturados , Insetos , Nutrientes , Aranhas , Animais , Insetos/metabolismo , Nutrientes/análise , Nutrientes/metabolismo , Aranhas/metabolismo , Ácidos Graxos Insaturados/metabolismoRESUMO
AIMS/HYPOTHESIS: The aim of this study was to investigate how diabetes mellitus affects longer term outcomes in individuals presenting to hospital with non-ST segment elevation myocardial infarction (NSTEMI). METHODS: We analysed data from 456,376 adults hospitalised between January 2005 and March 2019 with NSTEMI from the UK Myocardial Ischaemia National Audit Project (MINAP) registry, linked with Office for National Statistics death reporting. We compared outcomes and quality of care by diabetes status. RESULTS: Individuals with diabetes were older (median age 74 vs 73 years), were more often of Asian ethnicity (13% vs 4%) and underwent revascularisation (percutaneous coronary intervention or coronary artery bypass graft surgery) (38% vs 40%) less frequently than those without diabetes. The mortality risk for those with diabetes compared with those without was significantly higher at 30 days (HR 1.19, 95% CI 1.15, 1.23), 1 year (HR 1.28, 95% CI 1.26, 1.31), 5 years (HR 1.36, 95% CI 1.34, 1.38) and 10 years (HR 1.39, 95% CI 1.36, 1.42). In individuals with diabetes, higher quality inpatient care, assessed by opportunity-based quality indicator (OBQI) score category ('poor', 'fair', 'good' or 'excellent'), was associated with lower mortality rates compared with poor care (good: HR 0.74, 95% CI 0.73, 0.76; excellent: HR 0.69, 95% CI 0.68, 0.71). In addition, compared with poor care, excellent care in the diabetes group was associated with the lowest mortality rates in the diet-treated and insulin-treated subgroups (diet-treated: HR 0.64, 95% CI 0.61, 0.68; insulin-treated: HR 0.69, CI 0.66, 0.72). CONCLUSION/INTERPRETATION: Individuals with diabetes experience disparities during inpatient care following NSTEMI. They have a higher risk of long-term mortality than those without diabetes, and higher quality inpatient care may lead to better long-term survival.
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Introduction: Scapholunate instability is one of the most frequent types of wrist instability, but optimal management is not established. This research aims to identify current conservative management strategies for stage-one scapholunate instability and how these interventions are evaluated in the UK. Methods: A cross-sectional online survey of UK physiotherapists and occupational therapists with self-reported experience in the rehabilitation of stage-one scapholunate instability (ReSOS), was developed using the CROSS guideline and a clinical vignette. The frequency of treatment strategies was collated via a five-point Likert-type scale and evaluation strategies via fixed-response answers at three-to-six, seven-to-eleven and after 12 weeks post-injury. Data were analysed descriptively. Results: Forty-three electronic surveys were completed and analysed. Thirty physiotherapists and 13 occupational therapists responded, with 90% working in the NHS. Activity advice and education was the most frequently used treatment at all time-points (100%, 98%, 98%). Quick-DASH was most frequently used region-specific patient reported outcome measure at all time-points (72%, 60%, 67%). Discussion: Despite some identified themes, including neuromuscular rehabilitation strategies, the supporting evidence is limited in the ReSOS. It is unclear what rehabilitation and evaluation strategies are optimal and the development of a consensus on best practice is recommended.
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In-stent restenosis (ISR) still occur after percutaneous coronary intervention (PCI). Few studies have compared outcomes after PCI for de novo stenosis and ISR and the results are conflicting. The aim of the present study is to compare outcomes after PCI for ISR and de novo coronary stenosis. Using patient level data from the randomized all-comer SORT OUT studies III-X, we included all patients with previous PCI and either an ISR or a de novo lesion as the study target lesion. Outcomes of interest were major adverse cardiac events (MACE) and target lesion revascularization (TLR) after 5 years. Of the 2928 patients with a previous PCI included in the SORT OUT studies, 491 (17%) were treated for ISR and 2437 (83%) for a de novo stenosis. Baseline characteristics did not differ significantly. At 5 years, MACE occurred in 148 patients (32%) in the ISR group and in 654 patients (28%) in the de novo stenosis group (Crude and adjusted HR 1.16 (0.97-1.38) and 1.16 (0.97-1.38)). The risk of TLR was higher in the ISR group when compared to the de novo stenosis group (Crude and adjusted HR 1.64 (95% CI, 1.24-2.17) and 1.71 (95% CI, 1.27-2.30)). In conclusion, the risk of MACE was similar after PCI of ISR and de novo lesions after 5 years. However, the risk of TLR was higher in the ISR group compared to the de novo stenosis group.
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Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death (SCD) and improve survival in patients with a history of life-threatening arrhythmia or sudden cardiac arrest, and in select populations at high risk of SCD due to ventricular arrhythmias. However, patients with ICDs may receive inappropriate or unnecessary shocks, which have been associated with pro-arrhythmia, psychological sequelae, poor quality of life, and increased mortality. The benefits and risks of ICD therapy are therefore directly impacted on by physician operative and programming decisions. This article aims to provide a detailed review of transvenous ICD programming as guided by clinical trials.
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Desfibriladores Implantáveis , Humanos , Morte Súbita Cardíaca/prevenção & controle , Arritmias Cardíacas/terapiaRESUMO
Iron is the most abundant transition metal in the interstellar medium (ISM), and is thought to be involved in a variety of astrochemical processes. Here, we present the infrared multiple photon dissociation (IRMPD) spectra of Ar1,2FeH+ and their deuterated isotopologues in the region of 2240-14 000 cm-1. The Fe-H overtone stretching mode in ArFeH+ and Ar2FeH+ is observed at 3636 ± 28 cm-1 and 3659 ± 13 cm-1, respectively. Deuteration shifts these bands to 2618 ± 31 cm-1 and 2650 ± 14 cm-1 in ArFeD+ and Ar2FeD+, respectively. Additionally, the spectra of Ar2FeH+ and Ar2FeD+ feature broad transitions at â¼2200-4000 cm-1 and â¼4500-6500 cm-1. We assign these bands to electronic transitions from the thermally populated X5A2/X'5A1 ground state manifold into the A'5B2 and B5A1 states, which we model with multi-reference quantum chemical calculations including spin-orbit coupling. The calculations show that these transitions are symmetry forbidden in FeH+ and in the equilibrium geometry of ArFeH+/ArFeD+, while the zero-point oscillation of the bending mode of the triatomic molecule leads to some oscillator strength. Upon addition of the second argon atom, the transitions become weakly allowed in the equilibrium geometry of Ar2FeH+/Ar2FeD+ due to symmetry reduction from C∞v to C2v.
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PURPOSE: The study investigates the serial mediation of psychological ownership and workplace innovation in the nexus between organizational leadership and employee performance among healthcare workers in Ghana. DESIGN/METHODOLOGY/APPROACH: Six hundred and thirty-seven samples were selected using convenience sampling technique. The data gathered using self-reported questionnaire were analyzed using SEM-PLS. FINDINGS: The findings reveal that organizational leadership directly improves healthcare employee's psychological ownership, workplace innovation and employee performance. Psychological ownership and workplace innovation separately and serially mediate the relationship between organizational leadership and healthcare employees' performance. PRACTICAL IMPLICATIONS: The study highlights the significant influence of organizational leadership, psychological ownership and workplace innovation on the performance of healthcare employees. Healthcare organizations ought to allocate resources toward leadership development strategies to foster a favorable work atmosphere that promotes innovation and enables employees to assume ownership of their tasks and contribute to continuing enhancement, ultimately leading to enhanced performance. ORIGINALITY/VALUE: This research is a pioneering study on serial mediation of psychological ownership and workplace behavior in the association between organizational leadership and performance in healthcare settings in Ghana.
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Liderança , Humanos , Gana , Masculino , Feminino , Inquéritos e Questionários , Adulto , Pessoal de Saúde/psicologia , Desempenho Profissional , Local de Trabalho/psicologia , Inovação Organizacional , Pessoa de Meia-Idade , Cultura Organizacional , Análise de MediaçãoRESUMO
BACKGROUND: Parascaris spp. represent a significant threat to equine health worldwide, particularly in foals. The long-term survival of parasites in the host necessitates persistent modulation of the host immune response. Intercellular communication achieved through the exchange of molecules via extracellular vesicles (EVs) released from the parasite could be a crucial factor in this regard. This study aimed to isolate and characterize EVs released by adult male and female Parascaris worms and conduct a proteomic analysis to identify sex-specific proteins and potential immunomodulatory factors. METHODS: Live adult Parascaris worms were collected, and EVs were isolated from spent culture media using differential ultracentrifugation. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size, concentration, and morphology of the isolated EVs. Proteins within the isolated EVs were analyzed using mass spectrometry-based proteomics (LC-MS/MS). RESULTS: Proteomic analysis revealed a total of 113 proteins in Parascaris EVs, with several proteins showing homology to known helminth exosome proteins and exhibiting immunomodulatory functions. Sex-specific differences in EV protein composition were observed, with a distinct abundance of C-type lectins in female EVs, suggesting potential sex-specific roles or regulation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed metabolic pathways shared between male and female Parascaris EVs, as well as differences in signal transduction, and cell growth and death pathways, indicating sex-specific variations. CONCLUSIONS: These findings imply that Parascaris EVs and their protein cargo are complex. This data potentially opens avenues for discovering innovative approaches to managing and understanding helminth infection.
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Ascaridoidea , Vesículas Extracelulares , Proteínas de Helminto , Proteômica , Animais , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/ultraestrutura , Feminino , Masculino , Cavalos , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética , Proteínas de Helminto/química , Doenças dos Cavalos/parasitologia , Espectrometria de Massas em Tandem , Infecções por Ascaridida/parasitologia , Infecções por Ascaridida/veterinária , Cromatografia LíquidaRESUMO
Bacillus thuringiensis crystal (Cry) proteins have been expressed in commercial transgenic crops for nearly 30 years, providing safe and effective control of insect pests and significantly reducing the application of hazardous chemical pesticides. B. thuringiensis crystal proteins have also been shown to target parasitic nematodes, including plant parasitic nematodes. Recently, transgenic soybean crops expressing Cry14Ab have been shown to provide control against the soybean cyst nematode Heterodera glycines, marking the first time a crystal protein is being commercialized in transgenic crops for control of a nematode pest. However, apart from H. glycines and the free-living nematode, Caenorhabditis elegans, the breadth of nematode activity of Cry14Ab, e.g., against gastrointestinal parasitic nematodes (GINs), has not been reported. Here we study the efficacy of Cry14Ab against a wide range of gastrointestinal nematode parasites (GINs) in vitro and in vivo. We find that Cry14Ab is effective in vitro against the barber's pole worm Haemonchus contortus larvae, small strongyles cyathostomin larvae, the hookworm Ancylostoma ceylanicum adults, the roundworm Ascaris suum L4 larvae, and the whipworm Trichuris muris adults. In rodents infected with GIN parasites, Cry14Ab is effective as an in vivo anthelmintic against the hookworms A. ceylanicum and N. americanus, against the mouse parasite Heligmosomoides polygyrus bakeri, and against the roundworm A. suum. Cry14Ab also variably reduces the reproduction of the whipworm T. muris in vivo. Using optimized profile Markov Models, we looked for other putative anthelmintic Cry proteins and, within this list, identified a Bt crystal protein, GenBank accession no. MF893203, that we produced and demonstrated intoxicated GINs. This protein, with 90% amino acid identity to Cry14Ab, is active against C. elegans, A. ceylanicum adults, and A. suum L4 larvae in vitro. MF893203 was given the official designation of Cry14Ac. Cry14Ac is also an effective in vivo anthelmintic against A. ceylanicum hookworms in hamsters and intestinal A. suum in mice. Taken together, our results demonstrate that Cry14Ab and Cry14Ac have wide therapeutic utility against GINs.
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Light enhances or disrupts circadian rhythms, depending on the timing of exposure. Circadian disruption contributes to poor health outcomes that increase mortality risk. Whether personal light exposure predicts mortality risk has not been established. We therefore investigated whether personal day and night light, and light patterns that disrupt circadian rhythms, predicted mortality risk. UK Biobank participants (N = 88,905, 62.4 ± 7.8 y, 57% female) wore light sensors for 1 wk. Day and night light exposures were defined by factor analysis of 24-h light profiles. A computational model of the human circadian pacemaker was applied to model circadian amplitude and phase from light data. Cause-specific mortality was recorded in 3,750 participants across a mean (±SD) follow-up period of 8.0 ± 1.0 y. Individuals with brighter day light had incrementally lower all-cause mortality risk (adjusted-HR ranges: 0.84 to 0.90 [50 to 70th light exposure percentiles], 0.74 to 0.84 [70 to 90th], and 0.66 to 0.83 [90 to 100th]), and those with brighter night light had incrementally higher all-cause mortality risk (aHR ranges: 1.15 to 1.18 [70 to 90th], and 1.21 to 1.34 [90 to 100th]), compared to individuals in darker environments (0 to 50th percentiles). Individuals with lower circadian amplitude (aHR range: 0.90 to 0.96 per SD), earlier circadian phase (aHR range: 1.16 to 1.30), or later circadian phase (aHR range: 1.13 to 1.20) had higher all-cause mortality risks. Day light, night light, and circadian amplitude predicted cardiometabolic mortality, with larger hazard ratios than for mortality by other causes. Findings were robust to adjustment for age, sex, ethnicity, photoperiod, and sociodemographic and lifestyle factors. Minimizing night light, maximizing day light, and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity.
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Ritmo Circadiano , Luz , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Ritmo Circadiano/fisiologia , Idoso , Estudos Prospectivos , Mortalidade , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
Tomato spotted wilt virus (TSWV) is an orthotospovirus that infects both plants and insect vectors. Understanding the protein localization and interactions is crucial for unraveling the infection cycle and host-virus interactions. We investigated and compared the localization of TSWV proteins. A change in localization over time was associated with the viral proteins that did not contain signal peptides and transmembrane domains such as N, NSs and NSm, however, this only occurred in the plant cells, not in the insect cells. The localization between plants and insects otherwise was consistent indicating a similar mechanism is utilized by the virus in both types of cells. We also tested the localization of the proteins during an active plant infection using free RFP as a marker to highlight the nucleus and cytoplasm. Voids in the cytoplasm were shown only during infection and N, NSs, NSm and to lesser extent, GN and GC, were surrounding these areas suggesting it may be a site of replication or morphogenesis. Furthermore, we tested the interactions of viral proteins using both bimolecular fluorescence complementation (BiFC) and membrane-based yeast two-hybrid (MbY2H) assays. These revealed self-interactions of NSm, N, GN, GC, and NSs. We also identified interactions between different TSWV proteins, indicating their roles and host interactions, such as between NSs and GC and N and GC which may be necessary during the replication and assembly processes respectively. This research expands our knowledge of TSWV infection and elaborates on the intricate relationships between viral proteins, cellular dynamics, and host responses.
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Introduction: The COVID-19 pandemic disrupted healthcare delivery and increased cardiovascular morbidity and mortality. This study assesses whether cardiovascular mortality rates in the US have recovered post-pandemic and examines the equity of this recovery across different populations. Methods: We analyzed data from the CDC WONDER database, covering US residents' mortality from 2018-2023. We focused on cardiovascular diseases, categorized by ischemic heart disease (IHD), heart failure (HF), hypertensive diseases (HTN), and cerebrovascular disease. Age-adjusted mortality rates were calculated for three periods: pre-COVID (2018-2019), during COVID (2020-2021), and post-COVID (2022-2023), stratified by demographic and geographic variables. Results: Cardiovascular age-adjusted mortality rates increased by 5.9% during the pandemic but decreased by 3.4% post-pandemic, resulting in a net increase of 2.4% compared to pre-COVID levels. When compared to pre COVID age-adjusted mortality rates, post COVID IHD mortality age-adjusted mortality rates decreased by 5.0%, while cerebrovascular and HTN age-adjusted mortality rates increased by 5.9% and 28.5%, respectively. Men and younger populations showed higher increases in cardiovascular Age-adjusted mortality rates. Geographic disparities were notable, with significant reductions in cardiovascular mortality in the Northeast and increases in states like Arizona and Oregon. Conclusion: The COVID-19 pandemic led to a surge in cardiovascular mortality, with partial recovery post-pandemic. Significant differences in mortality changes highlight the need for targeted healthcare interventions to address inequities across demographic and geographic groups.
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BACKGROUND: Strengths-based approaches to health care are often seen as an alternative to deficit-based approaches and are common in Aboriginal health settings. Despite this, there is little existing research that describes Aboriginal peoples' perspectives about the strengths of their communities. This paper describes cultural strengths and resources as understood by Aboriginal people living in western Sydney. METHODS: In-depth interviews were used to collect qualitative data from two communities on Dharug and Dharrawal Country in western Sydney Australia. Data come from a larger study, which focused on how cultural strengths supported sexual well-being. Fifty-two interviews were conducted with Aboriginal young people (aged 16-24 years) by trained peer interviewers. Additionally, 16 interviews with Aboriginal adults (25 years and older) were conducted by members of the research team. FINDINGS AND DISCUSSION: While opinions varied, four key areas of cultural strength were identified: (1) strong kinship relationships; (2) knowledge sharing; (3) shared experiences, identities, and values; and (4) knowing Country. Throughout these four themes, the sense of connection and belonging is viewed as an important overarching theme. CONCLUSION: Communities are not homogenous with regard to what they view as cultural strengths. Knowing Country and practising culture meant different things to different individuals while providing a similar sense of belonging, connection, and identity. SO WHAT: Health service providers, policies, and programs can use this information to understand the continuing impacts of past policies and events whilst recognising that each community has strengths that can be drawn upon to improve service engagement, knowledge sharing, and health outcomes.
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Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and emerging therapeutic target that is overexpressed in most castration-resistant prostate cancers and implicated as a driver of disease progression and resistance to hormonal therapies. Here we define the lineage-specific action and differential activity of EZH2 in both prostate adenocarcinoma and neuroendocrine prostate cancer (NEPC) subtypes of advanced prostate cancer to better understand the role of EZH2 in modulating differentiation, lineage plasticity, and to identify mediators of response and resistance to EZH2 inhibitor therapy. Mechanistically, EZH2 modulates bivalent genes that results in upregulation of NEPC-associated transcriptional drivers (e.g., ASCL1) and neuronal gene programs in NEPC, and leads to forward differentiation after targeting EZH2 in NEPC. Subtype-specific downstream effects of EZH2 inhibition on cell cycle genes support the potential rationale for co-targeting cyclin/CDK to overcome resistance to EZH2 inhibition.
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Proteína Potenciadora do Homólogo 2 de Zeste , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Masculino , Humanos , Linhagem Celular Tumoral , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Diferenciação Celular , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Camundongos , Linhagem da CélulaRESUMO
TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K2P) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K2P channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus "silent". Here we show that TASK-5 channels are indeed non-functional as homodimers, but are involved in the formation of functional channel complexes with TASK-1 and TASK-3. TASK-5 negatively modulates the surface expression of TASK channels, while the heteromeric TASK-5-containing channel complexes located at the plasma membrane are characterized by changes in single-channel conductance, Gq-coupled receptor-mediated channel inhibition, and sensitivity to TASK modulators. The unique pharmacology of TASK-1/TASK-5 heterodimers, affected by a common polymorphism in KCNK15, needs to be carefully considered in the future development of drugs targeting TASK channels. Our observations provide an access to study TASK-5 at the functional level, particularly in malignant cancers associated with KCNK15.
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Proteínas do Tecido Nervoso , Canais de Potássio de Domínios Poros em Tandem , Animais , Humanos , Membrana Celular/metabolismo , Células HEK293 , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Canais de Potássio de Domínios Poros em Tandem/genética , Multimerização ProteicaRESUMO
The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants by conducting a positron emission tomography (PET) study. 120-min PET scans using the 5-HT2A receptor agonist radiotracer [11C]Cimbi-36 were conducted at baseline and after oral doses of either 10, 20, or 40 mg of ketanserin; each participant underwent one or two scans after ketanserin administration. Occupancy was defined as the percent change in neocortex binding potential (BPND), estimated using the simplified reference tissue model (SRTM) with the cerebellum as reference region. Peroral ketanserin intake resulted in a plasma concentration-related increase in cerebral 5-HT2A receptor occupancy with the highest plasma ketanserin concentrations measured after â¼2 h. The relation between mean plasma ketanserin concentrations and 5-HT2A receptor occupancy conformed to a single-site binding model with an estimated EC50 (95 % CI) of 2.52 (0.75; 8.1) ng/mL, which corresponds to a peroral dose of ketanserin of approximately 10 mg. These data elucidate for the first time in humans the cerebral pharmacodynamics of ketanserin, both benefitting its use as a pharmacological tool for probing brain function and adding to its potential for therapeutic use in rescuing a bad psychedelic experience.