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Many organisms harbor heritable bacterial symbionts that offer context-specific benefits to their hosts. In some of these symbioses, symbionts live inside host cells as endosymbionts. Studying the biology of endosymbiosis is challenging because it is hard to independently cultivate hosts and endosymbionts. A recent study, using a simple defined growth medium at ambient temperature, established an axenic culture of the pea aphid's heritable bacterial endosymbiont, Candidatus Fukatsuia symbiotica (G. P. Maeda, M. K. Kelly, A. Sundar, and N. A. Moran, mBio 15:e03253-23, 2024, https://doi.org/10.1128/mbio.03253-23). Notably, the monoculture was capable of host recolonization, was stably transmitted, and returned similar host phenotypes to those observed in native infections. This advance in uncoupling the cultivation of an endosymbiont and its host opens avenues for genetic manipulation of the endosymbiont that will facilitate hypothesis-driven work to explore the mechanisms of host-endosymbiont biology and potentially facilitate the development of symbiont-mediated practical-application biotechnologies.
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Áfidos , Interacciones Microbiota-Huesped , Simbiosis , Animales , Áfidos/microbiología , Áfidos/fisiología , Bacterias/genética , Bacterias/crecimiento & desarrolloRESUMEN
Southern right whales (SRWs, Eubalaena australis) have been observed feeding both at and below the surface (< 10 m) in Golfo Nuevo (42°42' S, 64°30' W), Península Valdés, Argentina, an area traditionally recognized as calving ground. In addition, we documented diving feeding behavior in SRWs during their stay in this gulf, which has not been previously described. We assessed this behavior using suction-cup-attached video-imaging tags (CRITTERCAMs) on individual whales. A total of eight CRITTERCAM deployments were successful, and feeding events were documented in all SRWs successfully equipped with CRITTERCAMs. The highest speeds occurred during the ascent phase, and the average diving time was 6 min 45 s ± 3 min 41 s for SRWs. Concurrently, zooplankton samples were collected from the subsurface and bottom of the water in areas where tagged whales dived to assess differences in composition, abundance, and biomass. Copepods dominated the upper layer, while euphausiids were more abundant in the deeper sample. Furthermore, zooplankton total biomass was five times higher at depth (2515.93 mg/m3) compared to the subsurface (500.35 mg/m3). Differences in zooplankton characteristics between depths, combined with CRITTERCAM videos, indicated that SRWs exploit high concentrations of organisms near the seafloor during daytime feeding dives. This study provides baseline insights into how SRWs utilize Península Valdés during their stay in the area.
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Conducta Alimentaria , Ballenas , Zooplancton , Animales , Argentina , Zooplancton/fisiología , Ballenas/fisiología , Conducta Alimentaria/fisiología , Buceo , Conducta Predatoria/fisiologíaRESUMEN
PURPOSE: Clonal hematopoiesis of indeterminate potential (CHIP) is frequent in patients with solid tumors. Prospective data about CHIP prevalence at breast cancer diagnosis and its dynamic evolution under treatment selective pressure are limited. PATIENTS AND METHODS: We performed targeted error-corrected sequencing on 614 samples from 380 patients with breast cancer. We investigated the dynamics of CHIP on prospectively collected paired samples from patients with early breast cancer (eBC) receiving chemotherapy (CT) or endocrine therapy (ET). We assessed the correlation of CHIP with survival in patients with metastatic triple-negative breast cancer (mTNBC). We estimated the risk of progression to treatment-related myeloid neoplasms (t-MN) according to the clonal hematopoiesis risk score (CHRS). In exploratory analyses, we considered clonal hematopoiesis (CH) with variant allele fraction (VAF) ≥0.005. RESULTS: CHIP was identified in 15% of patients before treatment. Few CHIP emerged after treatment, and the risk of developing new mutations was similar for patients receiving CT versus ET (odds ratio [OR], 1.16; P = .820). However, CT increased the risk of developing new CH with VAF ≥0.005 (OR, 3.45; P = .002). Five TP53-mutant CH with VAF ≥0.005 emerged among patients receiving CT. Most patients had low risk of t-MN according to the CHRS score. CHIP did not correlate with survival in mTNBC. CONCLUSION: CHIP is frequent in patients with breast cancer. In this study, CT did not lead to emergence of new CHIP, and most patients had low risk of developing t-MN. This finding is reassuring, given long life expectancy of patients with eBC and the association of CHIP with morbidity and mortality. However, TP53-mutant CH with VAF ≥0.005 emerged with CT, which carries high risk of t-MN. Evolution of these small clones and their clinical significance warrant further investigation.
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First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the 'gold standard' knowledge resource for drug, drug-target and related pharmaceutical information. DrugBank is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug-drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug-food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug-drug interactions, drug-food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.
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Bases del Conocimiento , Metabolómica , Espectrometría de Masas en Tándem , Bases de Datos Factuales , Interacciones Alimento-DrogaRESUMEN
Organisms across the tree of life colonize novel environments by partnering with bacterial symbionts. These symbioses are characterized by intimate integration of host/endosymbiont biology at multiple levels, including metabolically. Metabolic integration is particularly important for sap-feeding insects and their symbionts, which supplement nutritionally unbalanced host diets. Many studies reveal parallel evolution of host/endosymbiont metabolic complementarity in amino acid biosynthesis, raising questions about how amino acid metabolism is regulated, how regulatory mechanisms evolve, and the extent to which similar mechanisms evolve in different systems. In the aphid/Buchnera symbiosis, the transporter ApGLNT1 (Acyrthosiphon pisum glutamine transporter 1) supplies glutamine, an amino donor in transamination reactions, to bacteriocytes (where Buchnera reside) and is competitively inhibited by Buchnera-supplied arginine-consistent with a role regulating amino acid metabolism given host demand for Buchnera-produced amino acids. We examined how ApGLNT1 evolved a regulatory role by functionally characterizing orthologs in insects with and without endosymbionts. ApGLNT1 orthologs are functionally similar, and orthology searches coupled with homology modeling revealed that GLNT1 is ancient and structurally conserved across insects. Our results indicate that the ApGLNT1 symbiotic regulatory role is derived from its ancestral role and, in aphids, is likely facilitated by loss of arginine biosynthesis through the urea cycle. Given consistent loss of host arginine biosynthesis and retention of endosymbiont arginine supply, we hypothesize that GLNT1 is a general mechanism regulating amino acid metabolism in sap-feeding insects. This work fills a gap, highlighting the broad importance of co-option of ancestral proteins to novel contexts in the evolution of host/symbiont systems.
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Áfidos , Buchnera , Animales , Glutamina/metabolismo , Áfidos/microbiología , Buchnera/genética , Buchnera/metabolismo , Aminoácidos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Arginina/metabolismo , Simbiosis/fisiologíaRESUMEN
BACKGROUND: Photoplethysmography (PPG) sensors, typically found in wrist-worn devices, can continuously monitor heart rate (HR) in large populations in real-world settings. Resting heart rate (RHR) is an important biomarker of morbidities and mortality, but no universally accepted definition nor measurement criteria exist. In this study, we provide a working definition of RHR and describe a method for accurate measurement of this biomarker, recorded using PPG derived from wristband measurement across the 24-hour cycle. METHODS: 433 healthy subjects wore a wrist device that measured activity and HR for up to 3 months. HR during inactivity was recorded and the duration of inactivity needed for HR to stabilise was ascertained. We identified the lowest HR during each 24-hour cycle (true RHR) and examined the time of day or night this occurred. The variation of HR during inactivity through the 24-hour cycle was also assessed. The sample was also subdivided according to daily activity levels for subset analysis. FINDINGS: Adequate data was obtained for 19,242 days and 18,520 nights. HR stabilised in most subjects after 4 minutes of inactivity. Mean (SD) RHR for the sample was 54.5 (8.0) bpm (day) and 50.5 (7.6) bpm (night). RHR values were highest in the least active group (lowest MET quartile). A circadian variation of HR during inactivity was confirmed, with the lowest values being between 0300 and 0700 hours for most subjects. INTERPRETATION: RHR measured using a PPG-based wrist-worn device is significantly lower at night than in the day, and a circadian rhythm of HR during inactivity was confirmed. Since RHR is such an important health metric, clarity on the definition and measurement methodology used is important. For most subjects, a minimum rest time of 4 minutes provides a reliable measurement of HR during inactivity and true RHR in a 24-hour cycle is best measured between 0300 and 0700 hours. Funding: This study was funded by Google.
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Recent discoveries have demonstrated that the physiological function of bile acids extends to the regulation of diverse signaling processes through interactions with nuclear and G protein-coupled receptors, most notably the Farnesoid-X nuclear receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Targeting such signaling pathways pharmacologically, i.e. with bile acid-derived therapeutics, presents great potential for the treatment of various metabolic, inflammatory immune, liver, and neurodegenerative diseases. Here we report the discovery of two potent and selective TGR5 agonists (NZP196 and 917). These compounds are the taurine conjugates of 6α-ethyl-substituted 12ß-methyl-18-nor-bile acids with the side chain being located on the α-face of the steroid scaffold. The compounds emerged from a screening effort of a diverse library of 12ß-methyl-18-nor-bile acids that were synthesized from 12ß-methyl-18-nor-chenodeoxycholic acid and its C17-epimer. Upon testing for FXR activity, both compounds were found to be inactive, thus revealing selectivity for TGR5.
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Ácidos y Sales Biliares , Receptores Acoplados a Proteínas G , Ácidos y Sales Biliares/farmacología , Receptores Acoplados a Proteínas G/agonistas , Transducción de Señal , Hígado/metabolismo , Ácido QuenodesoxicólicoRESUMEN
Quantifying the size of endosymbiont populations is challenging because endosymbionts are typically difficult or impossible to culture and commonly polyploid. Current approaches to estimating endosymbiont population sizes include quantitative PCR (qPCR) targeting endosymbiont genomic DNA and flow-cytometry. While qPCR captures genome copy number data, it does not capture the number of bacterial cells in polyploid endosymbiont populations. In contrast, flow cytometry can capture accurate estimates of whole host-level endosymbiont population size, but it is not readily able to capture data at the level of endosymbiotic host cells. To complement these existing approaches for estimating endosymbiont population size, we designed and implemented an object detection/segmentation tool for counting the number of endosymbiont cells in micrographs of host tissues. The tool, called SymbiQuant, which makes use of recent advances in deep neural networks includes a graphic user interface that allows for human curation of tool output. We trained SymbiQuant for use in the model aphid/Buchnera endosymbiosis and studied Buchnera population dynamics and phenotype over aphid postembryonic development. We show that SymbiQuant returns accurate counts of endosymbionts, and readily captures Buchnera phenotype. By replacing our training data with data composed of annotated microscopy images from other models of endosymbiosis, SymbiQuant has the potential for broad application. Our tool, which is available on GitHub, adds to the repertoire of methods researchers can use to study endosymbiosis at the organismal, genome, and now endosymbiotic host tissue or cell levels.
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Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure-activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro-furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.
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Ácidos y Sales Biliares , Ácido Quenodesoxicólico , Ácido Quenodesoxicólico/química , Oxidación-Reducción , Esteroides , Relación Estructura-ActividadRESUMEN
In the quest for new modulators of the Farnesoid-X (FXR) and Takeda G-protein-coupled (TGR5) receptors, bile acids are a popular candidate for drug development. Recently, bile acids endowed with a C16-hydroxy group emerged as ligands of FXR and TGR5 with remarkable agonistic efficacies. Inspired by these findings, we synthesised a series of C16-hydroxylated 12ß-methyl-18-nor-bile acid analogues from a Δ13(17)-12ß-methyl-18-nor-chenodeoxycholic acid intermediate (16), the synthesis of which we reported previously. The preparation of these aptly named 12ß-methyl-18-nor-avicholic acids (17, 18, 41 and 42) was accomplished via allylic oxidation at C16, hydrogenation of the C13âC17 double bond and selective reduction of the C16-carbonyl group. Described also are various side products which were isolated during the evaluation of methods to affect the initial allylic oxidation. In addition, C23-methyl modified 12ß-methyl-18-nor-bile acids with (48, 49, 51 and 52) and without a C16-hydroxy group (45, 46 and 55), were synthesized to enable comparison of biological activities between these compounds and their un-methylated counterparts. As a result of our investigations we identified (23R)-12ß,23-dimethyl-18-nor-chenodeoxycholic acid (46) and 12ß-methyl-17-epi-18-nor-chenodeoxycholic acid 53 as TGR5 ligands with EC50 values of 25 µM.
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Ácidos y Sales Biliares , Ácido Quenodesoxicólico , Ácidos y Sales Biliares/farmacología , Ácido Quenodesoxicólico/análogos & derivados , Hidrogenación , LigandosRESUMEN
Parkinson's Disease is the most common neurodegenerative movement disorder globally, with prevalence increasing. There is an urgent need for new therapeutics which are disease-modifying rather than symptomatic. Mitochondrial dysfunction is a well-documented mechanism in both sporadic and familial Parkinson's Disease. Furthermore, ursodeoxycholic acid (UDCA) has been identified as a bile acid which leads to increased mitochondrial function in multiple in vitro and in vivo models of Parkinson's Disease. Here, we describe the synthesis of novel C-nor-D-homo bile acid derivatives and the 12-hydroxy-methylated derivative of lagocholic acid (7) and their biological evaluation in fibroblasts from patients with either sporadic or LRRK2 mutant Parkinson's Disease. These compounds boost mitochondrial function to a similar level or above that of UDCA in many assays; notable, however, is their ability to boost mitochondrial function to a higher level and at lower concentrations than UDCA specifically in the fibroblasts from LRRK2 patients. Our study indicates that novel bile acid chemistry could lead to the development of more efficacious bile acids which increase mitochondrial function and ultimately cellular health at lower concentrations proving attractive potential novel therapeutics for Parkinson's Disease.
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Enfermedad de Parkinson , Humanos , Ácidos y Sales Biliares , Enfermedad de Parkinson/tratamiento farmacológico , Ácido Ursodesoxicólico/farmacología , Colanos/químicaRESUMEN
Decoupling the roles of the farnesoid X nuclear receptor and Takeda G-protein-coupled bile acid receptor 5 is essential for the development of novel bile acid therapeutics targeting metabolic and neurodegenerative diseases. Herein, we describe the synthesis of 12ß-methyl-18-nor-bile acids which may serve as probes in the search for new bile acid analogues with clinical applicability. A Nametkin-type rearrangement was applied to protected cholic acid derivatives, giving rise to tetra-substituted Δ13,14- and Δ13,17-unsaturated 12ß-methyl-18-nor-bile acid intermediates (24a and 25a). Subsequent catalytic hydrogenation and deprotection yielded 12ß-methyl-18-nor-chenodeoxycholic acid (27a) and its 17-epi-epimer (28a) as the two major reaction products. Optimization of the synthetic sequence enabled a chromatography-free route to prepare these bile acids at a multi-gram scale. In addition, the first cis-C-D ring-junctured bile acid and a new 14(13 â 12)-abeo-bile acid are described. Furthermore, deuteration experiments were performed to provide mechanistic insights into the formation of the formal anti-hydrogenation product 12ß-methyl-18-nor-chenodeoxycholic acid (27a).
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The aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host-plant associations, uncovering the widespread co-option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.
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Áfidos/genética , Evolución Molecular , Variación Genética , Genoma de los Insectos/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Animales , Áfidos/clasificación , Áfidos/fisiología , Secuencia de Bases , Genómica/métodos , Geografía , Interacciones Huésped-Parásitos/efectos de los fármacos , Mutación , Filogenia , Plantas/parasitología , Polimorfismo de Nucleótido Simple , Homología de Secuencia de Ácido NucleicoRESUMEN
BACKGROUND: Host/symbiont integration is a signature of evolutionarily ancient, obligate endosymbioses. However, little is known about the cellular and developmental mechanisms of host/symbiont integration at the molecular level. Many insects possess obligate bacterial endosymbionts that provide essential nutrients. To advance understanding of the developmental and metabolic integration of hosts and endosymbionts, we track the localization of a non-essential amino acid transporter, ApNEAAT1, across asexual embryogenesis in the aphid, Acyrthosiphon pisum. Previous work in adult bacteriomes revealed that ApNEAAT1 functions to exchange non-essential amino acids at the A. pisum/Buchnera aphidicola symbiotic interface. Driven by amino acid concentration gradients, ApNEAAT1 moves proline, serine, and alanine from A. pisum to Buchnera and cysteine from Buchnera to A. pisum. Here, we test the hypothesis that ApNEAAT1 is localized to the symbiotic interface during asexual embryogenesis. RESULTS: During A. pisum asexual embryogenesis, ApNEAAT1 does not localize to the symbiotic interface. We observed ApNEAAT1 localization to the maternal follicular epithelium, the germline, and, in late-stage embryos, to anterior neural structures and insect immune cells (hemocytes). We predict that ApNEAAT1 provisions non-essential amino acids to developing oocytes and embryos, as well as to the brain and related neural structures. Additionally, ApNEAAT1 may perform roles related to host immunity. CONCLUSIONS: Our work provides further evidence that the embryonic and adult bacteriomes of asexual A. pisum are not equivalent. Future research is needed to elucidate the developmental time point at which the bacteriome reaches maturity.
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OBJETIVOS: describir el comportamiento ocupacional en tiempos de pandemia, específicamente durante el aislamiento social obligatorio, e identificar su impacto en el equilibrio ocupacional de la población estudiada. MÉTODOS: investigación de tipo cualitativa, con un diseño descriptivo exploratorio, se realizó entrevistas semiestructuradas a personas de diversos rangos etarios subdivididos en infancia, jóvenes, personas adultas y personas mayores, todas habitantes de la ciudad de Punta Arenas que estuvieron en cuarentena total obligatoria en los meses de abril y mayo de 2020. RESULTADOS: se identificaron dos grandes categorías: primero: Adaptación ocupacional/satisfacción y bienestar, a partir de las cuales se generaron las siguientes subcategorías: Exploración ocupacional, balance ocupacional, elección ocupacional, eficacia, calidad de vida y aprendizajes; la segunda categoría se denomina desequilibrio ocupacional/insatisfacción o ausencia de bienestar, que incluye subcategorías tales como: tipo y cantidad de ocupaciones, desestructuración de patrones de ejecución, deprivación ocupacional, infraocupación, sobreocupación. CONCLUSIÓN: frente a la situación de confinamiento en pandemia, las personas pueden tener una respuesta adaptativa o desadaptativa dependiendo de sus recursos personales, contextuales, sociales y emocionales. La terapia ocupacional puede aportar estrategias para mejorar la calidad de vida de las personas en crisis sanitarias como la que se vive en la actualidad
OBJECTIVE: To describe the occupational behavior in a time of pandemic, especially during compulsory social isolation, and to identify its impact on the occupational balance of the population under study. METHODS: Qualitative research with a descriptive exploratory design. Semi-structured interviews were carried out among people of different age ranges sub-divided into childhood, youth, adults and the elderly, all inhabitants of the city of Punta Arenas, who were in mandatory total quarantine during the months of April and May 2020. RESULTS: Two main categories were identified being the first one: occupational adaptation / satisfaction and well-being, from which the following subcategories were generated: occupational exploration, occupational balance, occupational choice, efficacy, quality of life and learning. The second category was called occupational imbalance / dissatisfaction or absence of well-being, which included subcategories such as: type and number of occupations, disruption of performance patterns, occupational deprivation, underemployment, over-employment. CONCLUSION: Faced with the confinement situation in a pandemic, people can have an adaptive or maladaptive response depending on their personal, contextual, social and emotional resources. Occupational therapy can provide strategies to improve the quality of life of people in health crisis like the one we are living today
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Salud Laboral , Medicina del Trabajo/organización & administración , Pandemias/prevención & control , Cuarentena , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Aislamiento Social , Adaptación Psicológica , Chile , Investigación Cualitativa , Medicina del Trabajo/ética , Cuidadores/psicologíaRESUMEN
After cardiopulmonary bypass surgery, the incidence of immunoglobulin antibody (IgG)-mediated heparin-induced thrombocytopenia (HITS) reported in various studies ranges between 1 and 3% as reported by (Anna et al. in Int J Cardiol. 144:405-7, 2010). We report two patients who underwent off-pump coronary artery grafting and developed severe HITS, leading to catastrophic and rare thrombotic complications.
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Self-harm and mental health are inter-related issues that substantially contribute to the global burden of disease. However, measurement of these issues at the population level is problematic. Statistics on suicide can be captured in national cause of death data collected as part of the coroner's review process, however, there is a significant time-lag in the availability of such data, and by definition, these sources do not include non-fatal incidents. Although survey, emergency department, and hospitalisation data present alternative information sources to measure self-harm, such data do not include the richness of information available at the point of incident. This paper describes the mental health and self-harm modules within the National Ambulance Surveillance System (NASS), a unique Australian system for monitoring and mapping mental health and self-harm. Data are sourced from paramedic electronic patient care records provided by Australian state and territory-based ambulance services. A team of specialised research assistants use a purpose-built system to manually scrutinise and code these records. Specific details of each incident are coded, including mental health symptoms and relevant risk indicators, as well as the type, intent, and method of self-harm. NASS provides almost 90 output variables related to self-harm (i.e., type of behaviour, self-injurious intent, and method) and mental health (e.g., mental health symptoms) in the 24 hours preceding each attendance, as well as demographics, temporal and geospatial characteristics, clinical outcomes, co-occurring substance use, and self-reported medical and psychiatric history. NASS provides internationally unique data on self-harm and mental health, with direct implications for translational research, public policy, and clinical practice. This methodology could be replicated in other countries with universal ambulance service provision to inform health policy and service planning.
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Ambulancias/normas , Morbilidad , Conducta Autodestructiva/epidemiología , Espera Vigilante/normas , Técnicos Medios en Salud/normas , Australia/epidemiología , Codificación Clínica/estadística & datos numéricos , Auxiliares de Urgencia/normas , Servicio de Urgencia en Hospital/normas , Femenino , Conductas Relacionadas con la Salud/fisiología , Humanos , Masculino , Registros Médicos , Salud Mental , Conducta Autodestructiva/patología , Conducta Autodestructiva/prevención & controlRESUMEN
Although harmful consumption of alcohol and other drugs (both illicit and pharmaceutical) significantly contribute to global burden of disease, not all harms are captured within existing morbidity data sources. Indeed, harms occurring in the community may be missed or under-reported. This paper describes the National Ambulance Surveillance System, a unique Australian system for monitoring and mapping acute harms related to alcohol and other drug consumption. Data are sourced from paramedic electronic patient care records provided by ambulance services from across Australia. Coding occurs in a purpose-built system, by a team of specialised research assistants. Alcohol, and specific illicit and pharmaceutical drugs, rather than broad drug classes, are manually coded and the dataset is reviewed and cleaned prior to analysis. The National Ambulance Surveillance System is an ongoing, dynamic surveillance system of alcohol and other drug-related harms across Australia. The data includes more than 140 output variables per attendance, including individual substances, demographics, temporal, geospatial, and clinical data (e.g., Glasgow Coma Scale score, naloxone provision and response, outcome of attendance). The National Ambulance Surveillance System is an internationally unique population-level surveillance system of acute harms arising from alcohol and other drug consumption. Dissemination of National Ambulance Surveillance System data has been used to inform and evaluate policy approaches and potential points of intervention, as well as guide workforce development needs and clinical practice at the local and national level. This methodology could be replicated in other countries.
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Drogas Ilícitas/efectos adversos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Alcohol/epidemiología , Ambulancias , Australia/epidemiología , Codificación Clínica , Bases de Datos Factuales , Humanos , Registros Médicos , Medicamentos bajo Prescripción/efectos adversos , Administración de la SeguridadRESUMEN
A highly enantioselective, organocatalytic, and scalable synthesis of a very unusual cis-decalin-cis-hydrindane tricyclic diterpenoid system has been achieved. Despite the prevalent pharmacological space that the related trans,trans and trans,cis-systems occupy, there have been no reports of an asymmetric synthesis of the cis,cis systems in the literature until now. We demonstrate the flexibility of our approach not only through access to a diverse range of products, all of which are attained in exceptionally high selectivities, but also by showing their easy conversion to the corresponding trans,cis-system and other derivatives.