Empowering Women Living with HIV/AIDS in Vietnam: A Hybrid Online-Offline Intervention to Combat Stigma.

Women living with HIV/AIDS (WLHA) encounter numerous challenges, such as stigma and gender disparities, that hinder their access to care, especially in patriarchal societies like Vietnam. We developed a hybrid intervention with online and offline (in-person) components to empower WLHA in Vietnam. The intervention was pilot tested with 91 WLHA in Hanoi. During baseline and 4-month, study investigators delivered two in-person sessions, one Zoom session, and 15 weeks of Zalo (social media platform) discussions to enhance positive coping strategies, treatment utilization and adherence, and engagement of support from family and peers. The participants continued their Zalo discussions from 4-month to 6-month without investigators' involvement. Intervention outcomes, including active coping and perceived barriers to care, were evaluated at baseline, 4-, and 6-month surveys. Mixed-effects regression models showed that the participants' active coping significantly increased from baseline (50.5 ± 9.4) to 4-month (53.8 ± 6.2; p = 0.0001), although there was a slight decrease at 6-month (52.8 ± 7.2), the change from 4-month to 6-month was not significantly significant (p = 0.3256). There was a significant reduction in participants' perceived barriers to care, from 19.8 ± 5.2 at baseline to 17.4 ± 5.2 at 4-month (p < 0.0001), which remained stable at 17.8 ± 4.3 at 6-month (p < 0.0001 compared to baseline). This intervention presents a promising model to empower WLHA in Vietnam and potentially in similar global contexts. Future interventions could benefit from leveraging natural peer leaders and adopting a more person-centered approach to meet WLHA's varying needs.

Distribution and Population Genetic Structure of the Hau Giang Medaka, Oryzias haugiangensis, Along the East Coast of the Indochinese Peninsula.

The east coast of the Indochinese Peninsula is a well-known transition zone from subtropical to tropical systems, yet only a small number of studies have been conducted on the biogeography and phylogeography of aquatic organisms in this region. The Hau Giang medaka, Oryzias haugiangensis, was originally described from the Mekong Delta in southern Vietnam, and later reported also from southeastern Thailand, west of the Mekong Delta region. However, the species' full geographic range and population genetic structures remain unknown. Field surveys showed a widespread distribution of this species along the east coast of the Indochinese Peninsula, as far as northern Vietnam. A mitochondrial gene phylogeny and population genetic structure analysis using genome-wide single nucleotide polymorphisms revealed that the populations of O. haugiangensis are highly structuralized along the east coast of Vietnam, with the southernmost Mekong Delta population clearly separated from three populations north of central Vietnam. Further field collections are necessary to determine the boundary between the southern and northern populations, and the presence or absence of a hybrid zone.

Documentation for Assessing Pain in Postoperative Pain Management Pre- and Post-intervention.

PURPOSE: Although Norwegian law requires the documentation of patients' care processes, including pain assessment, research has shown that the quality of postoperative documentation for assessing pain does not meet an acceptable standard and requires improvement. The purpose of this study was to investigate whether an educational intervention can increase nurses' documentation of postoperative pain assessments, alter patients' opioid consumption, and ensure that patients have at least one documented Numeric Rating Scale (NRS) ≤3 at rest before being discharged. A secondary aim was to investigate whether the nurses' education and experience influenced their pain assessments. DESIGN: An observational study with a pre-post intervention. METHODS: The study following a pre-post design involved documenting pain assessments of 304 patients undergoing cancer surgeries in a postoperative unit at the Norwegian Radium Hospital, Oslo University Hospital. In an educational intervention, two 45-minutes teaching sessions within two weeks, addressed validated pain assessment tools and the documentation of pain assessment. Descriptive frequency analysis and partial correlation with Pearson's r - value were used, with P < .05 indicating significance. FINDINGS: Postintervention, pain assessments in general increased significantly from a mean of two times per patient to three times. Overall, the use of assessment tool Critical -Care Pain Observation Tool increased from 6.1% to 25.8%, opioid consumption increased in mean from 3.34 to 4.79 in milligram and the documentation at discharge increased from 81.4% to 91.4%. The documentation of nurses with more than 10 years' experience in the unit especially improved from 17.5% to 31.7%. CONCLUSIONS: Educational intervention and reminders about basic systematic pain assessment and the evaluation of pain measures improved nurses' documentation of postoperative pain management and documentation at discharge. The findings underscore the importance of regularly ensuring the quality of patients' treatment by systematically documenting nurses' clinical tasks and the outcome of patients' care.

Protein Characteristics and Bioactivity of Fish Protein Hydrolysates from Tra Catfish (Pangasius hypophthalmus) Side Stream Isolates.

Enzymatic hydrolysis is a novel method to recover highly potent bioactive fish protein hydrolysates (FPHs) from fish processing side-streams. The common way of producing FPHs directly from fish side-streams may be inappropriate due to the excess of lipids and pro-oxidants, especially in lipid-rich streams, as obtained from Tra catfish. This study aimed to optimise the hydrolysis conditions for a commercial enzyme (Alcalase® 2.4 L) (enzyme concentrate, temperature, and time) in FPH production from the fish protein isolate obtained from Tra catfish dark muscle (DM-FPI) using the pH-shift method. The degree of hydrolysis (DH), protein recovery (PR), and antioxidant properties, including DPPH radical scavenging activity (DPPH-RSA) and total reducing power capacity (TRPC), were measured to evaluate the effects of the hydrolysis conditions on the FPHs. Optimal hydrolysis was obtained at an enzyme/substrate protein ratio of 3% (v/w) and a hydrolysis temperature of 50 °C for 3 h. The FPHs obtained from different substrates, including DM-FPI, abdominal cut-off (ACO) FPI, and head and backbone blend (HBB) FPI, had similar DHs under these optimum conditions, ranging from 22.5% to 24.0%. However, the FPH obtained from abdominal cut-off isolate (ACO-FPH) showed the highest PR of 81.5 ± 4.3% and the highest antioxidant properties, with a DPPH-RSA of 86.1 ± 1.6% and a TRPC of 6.4 ± 0.4 equivalent mg vitamin C/g protein. The resulting FPHs present a natural source of antioxidants with great potential for food applications, especially the ACO-FPH. In addition, all FPHs had excellent amino acid profiles, indicating strong potential for their use as supplements. Tra catfish protein-rich side-streams can thus be processed into high-value bioactive FPHs using Alcalase for human consumption.

New Surveillance Metrics for Alerting Community-Acquired Outbreaks of Emerging SARS-CoV-2 Variants Using Imported Case Data: Bayesian Markov Chain Monte Carlo Approach.

BACKGROUND: Global transmission from imported cases to domestic cluster infections is often the origin of local community-acquired outbreaks when facing emerging SARS-CoV-2 variants. OBJECTIVE: We aimed to develop new surveillance metrics for alerting emerging community-acquired outbreaks arising from new strains by monitoring the risk of small domestic cluster infections originating from few imported cases of emerging variants. METHODS: We used Taiwanese COVID-19 weekly data on imported cases, domestic cluster infections, and community-acquired outbreaks. The study period included the D614G strain in February 2020, the Alpha and Delta variants of concern (VOCs) in 2021, and the Omicron BA.1 and BA.2 VOCs in April 2022. The number of cases arising from domestic cluster infection caused by imported cases (Dci/Imc) per week was used as the SARS-CoV-2 strain-dependent surveillance metric for alerting local community-acquired outbreaks. Its upper 95% credible interval was used as the alert threshold for guiding the rapid preparedness of containment measures, including nonpharmaceutical interventions (NPIs), testing, and vaccination. The 2 metrics were estimated by using the Bayesian Monte Carlo Markov Chain method underpinning the directed acyclic graphic diagram constructed by the extra-Poisson (random-effect) regression model. The proposed model was also used to assess the most likely week lag of imported cases prior to the current week of domestic cluster infections. RESULTS: A 1-week lag of imported cases prior to the current week of domestic cluster infections was considered optimal. Both metrics of Dci/Imc and the alert threshold varied with SARS-CoV-2 variants and available containment measures. The estimates were 9.54% and 12.59%, respectively, for D614G and increased to 14.14% and 25.10%, respectively, for the Alpha VOC when only NPIs and testing were available. The corresponding figures were 10.01% and 13.32% for the Delta VOC, but reduced to 4.29% and 5.19% for the Omicron VOC when NPIs, testing, and vaccination were available. The rapid preparedness of containment measures guided by the estimated metrics accounted for the lack of community-acquired outbreaks during the D614G period, the early Alpha VOC period, the Delta VOC period, and the Omicron VOC period between BA.1 and BA.2. In contrast, community-acquired outbreaks of the Alpha VOC in mid-May 2021, Omicron BA.1 VOC in January 2022, and Omicron BA.2 VOC from April 2022 onwards, were indicative of the failure to prepare containment measures guided by the alert threshold. CONCLUSIONS: We developed new surveillance metrics for estimating the risk of domestic cluster infections with increasing imported cases and its alert threshold for community-acquired infections varying with emerging SARS-CoV-2 strains and the availability of containment measures. The use of new surveillance metrics is important in the rapid preparedness of containment measures for averting large-scale community-acquired outbreaks arising from emerging imported SARS-CoV-2 variants.

Covid-19 in America: Global supply chain reconsidered.

This research asks: To what extent has America's reliance on the global supply network aggravated the country's public health and economic crisis; and how did the American government respond to supply chain weaknesses during the early years of the Covid-19 pandemic? This study first assesses important conceptual considerations that explain the expansion of global value chains and the growth of trade interdependencies among nations. Next, an analytical case study observes (1) America's supply chain vulnerability through three major waves of infection, (2) the difficulty to mend weaknesses in the supply linkages once the novel coronavirus spread globally and (3) American government's failures to both anticipate and respond to supply shortages, especially in the health sector. Trump administration's policies failed to ensure a reliable supply of simple personal protective equipment (PPE) for healthcare professionals and hospitals throughout the first three waves of infection. Moreover, state and federal governments' substantial reliance on large manufacturers who have established procurement relationship with government led to continuous nationwide supply shortages throughout 2020. The federal government's inability to engage small and medium manufacturers in the production of critical supplies of PPE and diagnostic tests deepened and prolonged the devastating impacts of the pandemic. Our case study demonstrates that the American government needs to rethink the country's substantial reliance on the global supply chain, and the specific requirements to boost domestic manufacturing capacity. The revitalisation of America's manufacturing ability and the local supply networks will boost the productive power of the nation, strengthen resiliency, reduce vulnerability in disruptive times and prepare the nation for future crises.

Protein Recovery of Tra Catfish (Pangasius hypophthalmus) Protein-Rich Side Streams by the pH-Shift Method.

Increasing protein demand has led to growing attention being given to the full utilization of proteins from side streams in industrial fish processing. In this study, proteins were recovered from three protein-rich side streams during Tra catfish (Pangasius hypophthalamus) processing (dark muscle; head-backbone; and abdominal cut-offs) by an optimized pH-shift process. Physicochemical characteristics of the resulting fish protein isolates (FPIs) were compared to industrial surimi from the same raw material batch. The pH had a significant influence on protein extraction, while extraction time and the ratio of the extraction solution to raw material had little effect on the protein and dry matter recoveries. Optimal protein extraction conditions were obtained at pH 12, a solvent to raw material ratio of 8, and an extraction duration of 150 min. The resulting FPI contained <10% of the fat and <15% of the ash of the raw material, while the FPI protein recovery was 83.0−88.9%, including a good amino acid profile. All FPIs had significantly higher protein content and lower lipid content than the surimi, indicating the high efficiency of using the pH-shift method to recover proteins from industrial Tra catfish side streams. The FPI made from abdominal cut-offs had high whiteness, increasing its potential for the development of a high-value product.

Contributions to the biodiversity of Vietnam - Results of VIETBIO inventory work and field training in Cuc Phuong National Park.

VIETBIO [Innovative approaches to biodiversity discovery and characterisation in Vietnam] is a bilateral German-Vietnamese research and capacity building project focusing on the development and transfer of new methods and technology towards an integrated biodiversity discovery and monitoring system for Vietnam. Dedicated field training and testing of innovative methodologies were undertaken in Cuc Phuong National Park as part and with support of the project, which led to the new biodiversity data and records made available in this article collection. VIETBIO is a collaboration between the Museum für Naturkunde Berlin - Leibniz Institute for Evolution and Biodiversity Science (MfN), the Botanic Garden and Botanical Museum, Freie Universität Berlin (BGBM) and the Vietnam National Museum of Nature (VNMN), the Institute of Ecology and Biological Resources (IEBR), the Southern Institute of Ecology (SIE), as well as the Institute of Tropical Biology (ITB); all Vietnamese institutions belong to the Vietnam Academy of Science and Technology (VAST). The article collection "VIETBIO" (https://doi.org/10.3897/bdj.coll.63) reports original results of recent biodiversity recording and survey work undertaken in Cuc Phuong National Park, northern Vietnam, under the framework of the VIETBIO project. The collection consist of this "main" cover paper - characterising the study area, the general project approaches and activities, while also giving an extensive overview on previous studies from this area - followed by individual papers for higher taxa as studied during the project. The main purpose is to make primary biodiversity records openly available, including several new and interesting findings for this biodiversity-rich conservation area. All individual data papers with their respective primary records are expected to provide useful baselines for further taxonomic, phylogenetic, ecological and conservation-related studies on the respective taxa and, thus, will be maintained as separate datasets, including separate GUIDs also for further updating.

Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines as potent and selective agonists of the 5-HT2C receptor.

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines were identified as potent and selective agonists of the 5-HT2C receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, (R)-4-(3,3,3-trifluoropropyl)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.

Bacterial biofilm in adenoids of children with chronic otitis media. Part II: a case-control study of nasopharyngeal microbiota, virulence, and resistance of biofilms in adenoids.

Background: We previously described that adenoid tissue in children with chronic otitis media (COM) contained more mucosal biofilms than adenoid tissue removed for hypertrophy.Aims/objectives: The aim of the second part was to characterize nasopharyngeal microbiota and explore virulence of the most common middle ear pathogens.Material and methods: Bacteriological analysis was performed following a culture-based approach on the samples recovered from 30 patients of COM group (15 biofilm-positive and 15 biofilm-negative) and from 30 patients of a control group (15 biofilm-positive and 15 biofilm-negative). Virulence factors of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae were investigated.Results: The most frequent species were Firmicutes followed by Proteobacteria and Actinobacteria. The presence of biofilm was statistically associated with an increase of the number of bacterial species and Firmicutes phylum regardless of the condition (case/control). No virulence factors associated with invasive isolates were found for the most common middle ear pathogens.Conclusions and significance: This case-control study demonstrated that the presence of COM plus biofilm was associated with a given microbiota which contained more Firmicutes. Our study allows a better understanding of physiopathological mechanisms involved in chronic otitis media and paves the way for further investigations.

Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays.

A series of potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT2C receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat.

Direct Access to Acyl Fluorides from Carboxylic Acids Using a Phosphine/Fluoride Deoxyfluorination Reagent System.

A fast and simple method for deoxyfluorination of carboxylic acids is presented. The protocol employs commodity chemicals (PPh3, NBS, fluoride), affording products in excellent yields under mild conditions. Acyloxyphosphonium ion, the key reaction intermediate, was identified by NMR spectroscopic methods. Brønsted acidic conditions are essential for efficient C-F bond formation. The protocol displays scalability, high functional group tolerance, chemoselectivity, and easy purification of products. Deoxyfluorination of active pharmaceutical ingredients was established.

Oxidation-Resistant, Cost-Effective Epoxide-Modified Polyamine Adsorbents for CO2 Capture from Various Sources Including Air.

CO2 adsorbents based on the reaction of pentaethylenehexamine (PEHA) or tetraethylenepentamine (TEPA) with propylene oxide (PO) were easily prepared in "one pot" by impregnation on a silica support in water. The starting materials were readily available and inexpensive, facilitating the production of the adsorbents on a large scale. The prepared polyamine/epoxide adsorbents were efficient in capturing CO2 and could be regenerated under mild conditions (50-85 °C). They displayed a much-improved stability compared with their unmodified amine counterparts, especially under oxidative conditions. Leaching of the active organic amine became minimal or nonexistent after treatment with the epoxide. The adsorption as well as desorption kinetics were also greatly improved. The polyamine/epoxide adsorbents were able to capture CO2 from various sources including ambient air and indoor air with CO2 concentrations of only 400-1000 ppm. The presence of water, far from being detrimental, increased the adsorption capacity. Their use for indoor air quality purposes was explored.

Bacterial biofilm in adenoids of children with chronic otitis media. Part I: a case control study of prevalence of biofilms in adenoids, risk factors and middle ear biofilms.

BACKGROUND: Biofilms are communities of bacteria embedded in a self-produced glycocalyx matrix. Adenoids have been shown to harbor bacterial biofilms. Aim/objectives: To compare the prevalence of biofilms in adenoid of children with chronic otitis media (COM) (group1) versus a control group without any COM (group 2) having adenoids removed because of hypertrophy. MATERIAL AND METHODS: One hundred and three children were prospectively enrolled in this case-control study, group 1 (n = 52) and group 2 (n = 51). The main outcome measurement was the prevalence of biofilm in adenoidectomy specimens analyzed using confocal laser scanning microscopy. Children in group 1 who had middle ear (ME) effusion and requiring the insertion of a tympanostomy tube underwent biopsy of the ME mucosa and effusion sampling. RESULTS: Biofilms were found in adenoids' specimens of both groups and in the ME biopsy and effusion. The biofilm prevalence in adenoids was 63.5% (33/52) in group 1 and 47.1% (24/51) in group 2. Day nursery and previous antibiotics intake were significantly more frequent in group 1 than in group 2. CONCLUSIONS AND SIGNIFICANCE: This case-control study demonstrates that adenoid tissue in children with COM contains more mucosal biofilms than adenoid tissue removed for hypertrophy. Biofilm was seen in ME biopsies and effusion.

Evidence of Pure Spin-Current Generated by Spin Pumping in Interface-Localized States in Hybrid Metal-Silicon-Metal Vertical Structures.

Due to the difficulty of growing high-quality semiconductors on ferromagnetic metals, the study of spin diffusion transport in Si was limited to lateral geometry devices. In this work, by using an ultrahigh-vacuum wafer-bonding technique, we have successfully fabricated metal-semiconductor-metal CoFeB/MgO/Si/Pt vertical structures. We hereby demonstrate pure spin-current injection and transport in the perpendicular current flow geometry over a distance larger than 2 µm in n-type Si at room temperature. In those experiments, a pure propagating spin current is generated via ferromagnetic resonance spin pumping and converted into a measurable voltage by using the inverse spin Hall effect occurring in the top Pt layer. A systematic study varying both Si and MgO thicknesses reveals the important role played by the localized states at the MgO-Si interface for the spin-current generation. Proximity effects involving indirect exchange interactions between the ferromagnet and the MgO-Si interface states appears to be a prerequisite to establishing the necessary out-of-equilibrium spin population in Si under the spin-pumping action.

Stability of Golden redfish (Sebastes marinus) during frozen storage as affected by raw material freshness and season of capture.

Physicochemical changes of Icelandic golden redfish (Sebastes marinus) as affected by seasonal variation (June and November) and raw material freshness (processed 4 and 9 days postcatch) during frozen storage (at -25°C for 20 months) were studied to find optimal conditions for production of high-quality frozen products. Thawing loss, cooking yield, and color of the fillets as well as chemical composition, water holding capacity, pH, total volatile basic nitrogen, lipid oxidation, and hydrolysis of the light and dark muscle were analyzed every 4 months of frozen storage. Lipid hydrolysis was the main degradation process in the light muscle, while the dark muscle was more affected by lipid oxidation. Fish caught in November showed greater instability in the analyzed parameters during storage than fish caught in June, which could be linked to differences in individual poly unsaturated fatty acids between the two seasons. The quality attributes of fish processed on day 9 were similar to fish processed 4 days postcatch, except slightly higher thawing loss and yellowness, were observed in fish processed 9 days postcatch. Stability of golden redfish through frozen storage was higher in the fish caught in June than in November.

Validation of Questionnaire and Diary Measures of Time Outdoors Against an Objective Measure of Personal Ultraviolet Radiation Exposure.

Self-reported sun exposure is commonly measured using questionnaires or diaries, but there are limited data on their validity, particularly for population subgroups. This research aimed to compare self-reported sun exposure, measured as (1) habitual time outdoors over the past month on weekends and weekdays and (2) a 4-day diary measure, against objective measurement of personal ultraviolet radiation using polysulfone film dosimeters. From November 2015 to January 2016, 94 people (22-69 years and living in New South Wales, Australia) completed a questionnaire, 4-day diary and 4-day dosimeter measures of overall, weekday and weekend sun exposure. Spearman correlations and Bland-Altman plots were used to measure agreement. The overall weekly correlation was 0.57 (95% confidence interval [CI] 0.44, 0.68) between standard erythemal doses (SEDs) measured by dosimeter and time spent outdoors measured by questionnaire, 0.74 (95% CI 0.66-0.81) between dosimeter and diary, and 0.59 (95% CI 0.48-0.68) between questionnaire and diary measures. Validity was lower for younger people and weekend sun exposure. There was strong correlation between dosimeter and sun diary measures and moderate correlation between dosimeter and questionnaire measures. Daily measurement over a longer period may be required to accurately capture weeklong sun exposure in all population subgroups.

Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT2C receptor.

The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT2C receptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT2B receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT2C agonists were identified.

Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists.

The design and synthesis of novel 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamide CB2 selective ligands for the potential treatment of pain is described. Compound (R,R)-25 has good balance between CB2 agonist potency and selectivity over CB1, and possesses overall favorable pharmaceutical properties. It also demonstrated robust in vivo efficacy mediated via CB2 activation in the rodent models of inflammatory and osteoarthritis pain after oral administration.

Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration.

The kinetics of drug-receptor interactions can profoundly influence in vivo and in vitro pharmacology. In vitro, the potencies of slowly associating agonists may be underestimated in assays capturing transient signaling events. When divergent receptor-mediated signaling pathways are evaluated using combinations of equilibrium and transient assays, potency differences driven by kinetics may be erroneously interpreted as biased signaling. In vivo, drugs with slow dissociation rates may display prolonged physiologic effects inconsistent with their pharmacokinetic profiles. We evaluated a panel of 5-hydroxytryptamine2B (5-HT2B) receptor agonists in kinetic radioligand binding assays and in transient, calcium flux assays, and inositol phosphate accumulation assays; two functional readouts emanating from Gαq-mediated activation of phospholipase C. In binding studies, ergot derivatives demonstrated slow receptor association and dissociation rates, resulting in significantly reduced potency in calcium assays relative to inositol phosphate accumulation assays. Ergot potencies for activation of extracellular signal-regulated kinases 1 and 2 were also highly time-dependent. A number of ergots produced wash-resistant 5-HT2B signaling that persisted for many hours without appreciable loss of potency, which was not explained simply by slow receptor-dissociation kinetics. Mechanistic studies indicated that persistent signaling originated from internalized or sequestered receptors. This study provides a mechanistic basis for the long durations of action in vivo and wash-resistant effects in ex vivo tissue models often observed for ergots. The 5-HT2B agonist activity of a number of ergot-derived therapeutics has been implicated in development of cardiac valvulopathy in man. The novel, sustained nature of ergot signaling reported here may represent an additional mechanism contributing to the valvulopathic potential of these compounds.