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1.
Nat Plants ; 9(8): 1236-1251, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37563460

RESUMEN

Common buckwheat, Fagopyrum esculentum, is an orphan crop domesticated in southwest China that exhibits heterostylous self-incompatibility. Here we present chromosome-scale assemblies of a self-compatible F. esculentum accession and a self-compatible wild relative, Fagopyrum homotropicum, together with the resequencing of 104 wild and cultivated F. esculentum accessions. Using these genomic data, we report the roles of transposable elements and whole-genome duplications in the evolution of Fagopyrum. In addition, we show that (1) the breakdown of heterostyly occurs through the disruption of a hemizygous gene jointly regulating the style length and female compatibility and (2) southeast Tibet was involved in common buckwheat domestication. Moreover, we obtained mutants conferring the waxy phenotype for the first time in buckwheat. These findings demonstrate the utility of our F. esculentum assembly as a reference genome and promise to accelerate buckwheat research and breeding.


Asunto(s)
Fagopyrum , Fagopyrum/genética , Domesticación , Fitomejoramiento , Mapeo Cromosómico , Secuencia de Bases
2.
Sci Rep ; 13(1): 5013, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973465

RESUMEN

Hydrocarbon-degrading bacteria, which can be found living with eukaryotic phytoplankton, play a pivotal role in the fate of oil spillage to the marine environment. Considering the susceptibility of calcium carbonate-bearing phytoplankton under future ocean acidification conditions and their oil-degrading communities to oil exposure under such conditions, we investigated the response of non-axenic E. huxleyi to crude oil under ambient versus elevated CO2 concentrations. Under elevated CO2 conditions, exposure to crude oil resulted in the immediate decline of E. huxleyi, with concomitant shifts in the relative abundance of Alphaproteobacteria and Gammaproteobacteria. Survival of E. huxleyi under ambient conditions following oil enrichment was likely facilitated by enrichment of oil-degraders Methylobacterium and Sphingomonas, while the increase in relative abundance of Marinobacter and unclassified Gammaproteobacteria may have increased competitive pressure with E. huxleyi for micronutrient acquisition. Biodegradation of the oil was not affected by elevated CO2 despite a shift in relative abundance of known and putative hydrocarbon degraders. While ocean acidification does not appear to affect microbial degradation of crude oil, elevated mortality responses of E. huxleyi and shifts in the bacterial community illustrates the complexity of microalgal-bacterial interactions and highlights the need to factor these into future ecosystem recovery projections.


Asunto(s)
Petróleo , Petróleo/toxicidad , Petróleo/metabolismo , Dióxido de Carbono/metabolismo , Ecosistema , Concentración de Iones de Hidrógeno , Acidificación de los Océanos , Agua de Mar/microbiología , Bacterias/metabolismo , Hidrocarburos/metabolismo , Fitoplancton/metabolismo
3.
PLoS One ; 17(10): e0273015, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36190945

RESUMEN

A narrative systematic literature review was conducted to explore resilient performance in defence and security settings. A search strategy was employed across a total of five databases, searching published articles from 2001 onwards that assessed performance and optimal function in relation to resilience, in defence and security personnel. Following narrative synthesis, studies were assessed for quality. Thirty-two articles met inclusion criteria across a range of performance domains, including, but not limited to, course selection, marksmanship, land navigation, and simulated captivity. Some of the key findings included measures of mental toughness, confidence, and a stress-is-enhancing mindset being positively associated with performance outcomes. There was mixed evidence for the predictive value of biomarkers, although there was some support for cortisol, dehydroepiandrosterone sulfate (DHEA-S) and neuropeptide-y (NPY), and vagal reactivity. Interventions to improve resilient performance were focused on mindfulness or general psychological skills, with effects generally clearer on cognitive tasks rather than direct performance outcomes in the field. In sum, no single measure, nor intervention was consistently associated with performance over a range of domains. To inform future work, findings from the present review have been used to develop a framework of resilient performance, with the aim to promote theoretically informed work.


Asunto(s)
Atención Plena , Neuropéptidos , Biomarcadores , Sulfato de Deshidroepiandrosterona , Hidrocortisona
4.
J Pathol Clin Res ; 8(4): 395-407, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35257510

RESUMEN

In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non-MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non-contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.


Asunto(s)
Neoplasias , Algoritmos , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética
5.
J Rural Health ; 37(3): 645-654, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32602978

RESUMEN

PURPOSE: Accessibility and availability of health care services/providers is an increasing concern for many regional communities, particularly regional South Australia. Assessing the level of health service/provider utilization within a region (ie, expressed demand) can be useful in determining health care need and health service/workforce demand. METHODS: The regional South Australia health (RESONATE) survey aimed to determine the expressed demand for health care services and the health workforce in a regional South Australian population. The study was open to adults living in regional South Australia and was promoted using a comprehensive multimodal recruitment campaign. Data were collected between April 2017 and March 2018 using the consumer utilization, expectations and experiences of healthcare instrument. FINDINGS: A total of 3,926 adults completed the questionnaire. Participants reported using 47 different health care providers in the previous 12 months. Whilst almost all (92.9%) participants had seen a general practitioner in the past 12 months, yoga instructors, chiropractors, pharmacists, and physiotherapists were visited most frequently. Proportionally fewer participants in more remote locations received conventional services/treatments, though a significantly greater proportion of those in more remote locations had received complementary medicine services/treatments (relative to inner regional areas). CONCLUSIONS: Findings of the RESONATE survey point to a high level of expressed demand for conventional and complementary health care services among study participants, possibly higher than that reported in the general population. Examining the extent to which the health needs of this and other regional populations are met should be the focus of further research to better inform future health workforce/services planning.


Asunto(s)
Servicios de Salud Rural , Adulto , Australia , Estudios Transversales , Atención a la Salud , Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Australia del Sur
6.
Mar Pollut Bull ; 135: 205-215, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30301032

RESUMEN

A distinctive feature of the Deepwater Horizon (DwH) oil spill was the formation of significant quantities of marine oil snow (MOS), for which the mechanism(s) underlying its formation remain unresolved. Here, we show that Alteromonas strain TK-46(2), Pseudoalteromonas strain TK-105 and Cycloclasticus TK-8 - organisms that became enriched in sea surface oil slicks during the spill - contributed to the formation of MOS and/or dispersion of the oil. In roller-bottle incubations, Alteromonas cells and their produced EPS yielded MOS, whereas Pseudoalteromonas and Cycloclasticus did not. Interestingly, the Cycloclasticus strain was able to degrade n-alkanes concomitantly with aromatics within the complex oil mixture, which is atypical for members of this genus. Our findings, for the first time, provide direct evidence on the hydrocarbon-degrading capabilities for these bacteria enriched during the DwH spill, and that bacterial cells of certain species and their produced EPS played a direct role in MOS formation.


Asunto(s)
Bacterias/metabolismo , Sedimentos Geológicos/microbiología , Contaminación por Petróleo , Agua de Mar/microbiología , Alcanos/metabolismo , Alteromonas/fisiología , Biodegradación Ambiental , Emulsiones/química , Golfo de México , Hidrocarburos/metabolismo , Petróleo/metabolismo
7.
Eur J Sport Sci ; 18(6): 872-881, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29870312

RESUMEN

The purpose of this study was to examine the direction and magnitude of the relationship between mental toughness and pain catastrophizing and to explore whether mindfulness mediated this relationship. The design of the study was cross-sectional using self-report data. We recruited 142 recreational cyclists (female = 32) via online cycling forums. We asked participants to complete measures of mental toughness, dispositional mindfulness, and pain catastrophizing. Following the initial screening of data and the identification of non-normality and outliers, we calculated robust correlations and regressions to examine the size and direction of effects. Results revealed that mindfulness partially mediated a moderate negative relationship between mental toughness and pain catastrophizing. These results are consistent with prior theory regarding positive traits and their negative association with pain catastrophizing. Unique contributions included showing that mental toughness and mindfulness are positively associated and that mindfulness is negatively associated with pain catastrophizing in this sample of cyclists.


Asunto(s)
Adaptación Psicológica , Atletas/psicología , Catastrofización , Atención Plena , Dolor/psicología , Adolescente , Adulto , Anciano , Ciclismo/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Encuestas y Cuestionarios , Adulto Joven
8.
Int J Nurs Stud ; 81: 8-13, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29425913

RESUMEN

BACKGROUND: Rates of manuscript retraction in academic journals are increasing. Papers are retracted because of scientific misconduct or serious error. To date there have been no studies that have examined rates of retraction in nursing and midwifery journals. DESIGN: A systematic review of Journal Citation Report listed nursing science journals. DATA SOURCES: The Medline database was searched systematically from January 1980 through July 2017, and www.retractionwatch.com was manually searched for relevant studies that met the inclusion criteria. REVIEW METHODS: Two researchers undertook title and abstract and full text screening. Data were extracted on the country of the corresponding author, journal title, impact factor, study design, year of retraction, number of citations after retraction, and reason for retraction. Journals retraction index was also calculated. RESULTS: Twenty-nine retracted papers published in nursing science journals were identified, the first in 2007. This represents 0.029% of all papers published in these journals since 2007. We observed a significant increase in the retraction rate of 0.44 per 10,000 publications per year (95% CI; 0.03-0.84, p = .037). There was a negative association between a journal's retraction index and impact factor with a significant reduction in retraction index of -0.57 for a one-point increase in impact factor (95% CI; -1.05 to -0.09, p = .022). Duplicate publication was the most common reason for retraction (n = 18, 58%). The mean number of citations manuscripts received after retraction was seven, the highest was 52. Most (n = 27, 93.1%) of the retracted papers are still available online (with a watermark indicating they are retracted). CONCLUSION: Compared to more established academic disciplines, rates of retraction in nursing and midwifery are low. Findings suggest that unsound research is not being identified and that the checks and balances incumbent in the scientific method are not working. In a clinical discipline, this is concerning and may indicate that research that should have been removed from the evidence base continues to influence nursing and midwifery care.


Asunto(s)
Partería , Investigación en Enfermería , Humanos , Factor de Impacto de la Revista , Retractación de Publicación como Asunto
9.
Environ Microbiol ; 19(7): 2843-2861, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28585283

RESUMEN

Phytoplankton have been shown to harbour a diversity of hydrocarbonoclastic bacteria (HCB), yet it is not understood how these phytoplankton-associated HCB would respond in the event of an oil spill at sea. Here, we assess the diversity and dynamics of the bacterial community associated with a natural population of marine phytoplankton under oil spill-simulated conditions, and compare it to that of the free-living (non phytoplankton-associated) bacterial community. While the crude oil severely impacted the phytoplankton population and was likely conducive to marine oil snow formation, analysis of the MiSeq-derived 16S rRNA data revealed dramatic and differential shifts in the oil-amended communities that included blooms of recognized HCB (e.g., Thalassospira, Cycloclasticus), including putative novel phyla, as well as other groups with previously unqualified oil-degrading potential (Olleya, Winogradskyella, and members of the inconspicuous BD7-3 phylum). Notably, the oil biodegradation potential of the phytoplankton-associated community exceeded that of the free-living community, and it showed a preference to degrade substituted and non-substituted polycyclic aromatic hydrocarbons. Our study provides evidence of compartmentalization of hydrocarbon-degrading capacity in the marine water column, wherein HCB associated with phytoplankton are better tuned to degrading crude oil hydrocarbons than that by the community of planktonic free-living bacteria.


Asunto(s)
Biodegradación Ambiental , Flavobacteriaceae/metabolismo , Petróleo/metabolismo , Fitoplancton/microbiología , Piscirickettsiaceae/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Rhodospirillaceae/metabolismo , Flavobacteriaceae/genética , Contaminación por Petróleo , Piscirickettsiaceae/genética , ARN Ribosómico 16S/genética , Rhodospirillaceae/genética
10.
J Sports Sci ; 34(12): 1132-40, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26406766

RESUMEN

The purpose of this study was to examine the relationship between mindfulness and 800-m personal best (PB) times through pain catastrophising and to see whether the magnitude and direction of the relationship depended on gender. One hundred and nine participants reported their gender, completed measures of mindfulness (MAAS) and pain catastrophising (PCS) and reported PB 800 m times that were standardised based on current world records. Results revealed moderate-sized relationships between the predictor variables and standardised 800 m PB. The size of these relationships reduced after we controlled for gender. The follow-up, conditional process analysis - revealed significant direct and indirect effects that confirmed that pain catastrophising partially mediated the relationship between mindfulness and 800 m PB and that gender moderated the indirect paths. The indirect path between mindfulness and pain catastrophising was consistent with existing literature. However, the path between pain catastrophising and standardised 800 m PB was positive for females and negative for males. The different direction of the relationship could suggest that pain catastrophising could be performance enhancing for females.


Asunto(s)
Atletas/psicología , Catastrofización/psicología , Atención Plena , Dolor/psicología , Carrera/psicología , Adulto , Femenino , Humanos , Masculino , Modelos Psicológicos , Encuestas y Cuestionarios , Atletismo/psicología , Adulto Joven
11.
Biodegradation ; 25(1): 153-65, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23670057

RESUMEN

The role of clay minerals in crude oil saturated hydrocarbon removal during biodegradation was investigated in aqueous clay/saturated hydrocarbon microcosm experiments with a hydrocarbon degrading microorganism community. The clay minerals used for this study were montmorillonite, palygorskite, saponite and kaolinite. The clay mineral samples were treated with hydrochloric acid and didecyldimethylammonium bromide to produce acid activated- and organoclays respectively which were used in this study. The production of organoclay was restricted to only montmorillonite and saponite because of their relative high CEC. The study indicated that acid activated clays, organoclays and unmodified kaolinite, were inhibitory to biodegradation of the hydrocarbon saturates. Unmodified saponite was neutral to biodegradation of the hydrocarbon saturates. However, unmodified palygorskite and montmorillonite were stimulatory to biodegradation of the hydrocarbon saturated fraction and appears to do so as a result of the clays' ability to provide high surface area for the accumulation of microbes and nutrients such that the nutrients were within the 'vicinity' of the microbes. Adsorption of the saturated hydrocarbons was not significant during biodegradation.


Asunto(s)
Silicatos de Aluminio/química , Petróleo/metabolismo , Bentonita/química , Biodegradación Ambiental , Cromatografía de Gases , Arcilla , Ácido Clorhídrico/química , Concentración de Iones de Hidrógeno , Caolín/química , Compuestos de Magnesio/química , Compuestos de Amonio Cuaternario/química , Compuestos de Silicona/química , Propiedades de Superficie
12.
Environ Sci Pollut Res Int ; 20(9): 6445-54, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23589240

RESUMEN

The compositional changes of saturates, aromatics, resins and asphaltenes (SARA) fractions in aqueous clay/oil microcosm experiments with a hydrocarbon-degrading microorganism community were analysed using Iatroscan. The clay mineral samples used in this study were organomontmorillonite, acid-activated montmorillonite and K, Ca, Zn and Cr montmorillonites produced by modifying the original montmorillonite sample. The evaluation and quantification of biodegradation and adsorption were carried out using a combination of the Iatroscan and gravimetric analysis. The SARA compositions in the presence of organomontmorillonite and acid-activated montmorillonite after incubation follow the same pattern in which the aromatic fraction is higher than the other fractions unlike in the presence of unmodified, K, Ca and Zn montmorillonites, where the saturates fraction is higher than the other fractions. Changes in SARA fractions due to biodegradation seemed to occur most in the presence of unmodified and calcium montmorillonites; hence, the removal of SARA fractions due to biodegradation was significant and enhanced in the presence of these two clay samples. However, biodegradation in the presence of organomontmorillonite and acid-activated and Cr montmorillonites was hindered. The study indicated that Cr montmorillonite adsorbed resins most, whereas Zn and K montmorillonites adsorbed aromatics most after incubation.


Asunto(s)
Silicatos de Aluminio/química , Biodegradación Ambiental , Petróleo/análisis , Adsorción , Arcilla , Concentración de Iones de Hidrógeno
13.
Am J Phys Anthropol ; 149(2): 283-90, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22961368

RESUMEN

There is a growing body of archaeobotanical evidence for the harvesting of millet in Eurasia prior to 5,000 cal. BC. Yet direct evidence for the extent of millet consumption in this time period is rare. This contradiction may be due to millet crops making only a minor contribution to the diet before 5,000 BC. In this article, drawing from recent excavations in North China, we present evidence for millet crops making a substantial contribution to human and animal diets in periods, which correspond chronologically with the time depth of the archaeobotanical record. We infer that in eastern Inner Mongolia, human adoption of millets, which may or may be not related to substantial agriculture, happened at the Early Neolithic, with direct dates between 5,800 and 5,300 cal. BC.


Asunto(s)
Agricultura/historia , Arqueología , Dieta/historia , Panicum/historia , Animales , Huesos/química , Isótopos de Carbono/análisis , China , Colágeno/química , Historia Antigua , Humanos , Isótopos de Nitrógeno/análisis
14.
Trials ; 12: 167, 2011 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-21726440

RESUMEN

BACKGROUND: The serious mental illness Health Improvement Profile [HIP] is a brief pragmatic tool, which enables mental health nurses to work together with patients to screen physical health and take evidence-based action when variables are identified to be at risk. Piloting has demonstrated clinical utility and acceptability. METHODS/DESIGN: A single blind parallel group cluster randomised controlled trial with secondary economic analysis and process observation. Unit of randomisation: mental health nurses [MHNs] working in adult community mental health teams across two NHS Trusts. SUBJECTS: Patients over 18 years with a diagnosis of schizophrenia, schizoaffective or bipolar disorder on the caseload of participating MHNs. PRIMARY OBJECTIVE: To determine the effects of the HIP programme on patients' physical wellbeing assessed by the physical component score of the Medical Outcome Study (MOS) 36 Item Short Form Health Survey version 2 [SF-36v2]. SECONDARY OBJECTIVES: To determine the effects of the HIP programme on: cost effectiveness, mental wellbeing, cardiovascular risk, physical health care attitudes and knowledge of MHNs and to determine the acceptability of the HIP Programme in the NHS. Consented nurses (and patients) will be randomised to receive the HIP Programme or treatment as usual. Outcomes will be measured at baseline and 12 months with a process observation after 12 months to include evaluation of patients' and professionals' experience and observation of any effect on care plans and primary-secondary care interface communication. Outcomes will be analysed on an intention-to-treat (ITT) basis. DISCUSSION: The results of the trial and process observation will provide information about the effectiveness of the HIP Programme in supporting MHNs to address physical comorbidity in serious mental illness. Given the current unacceptable prevalence of physical comorbidity and mortality in the serious mental illness population, it is hoped the HIP trial will provide a timely contribution to evidence on organisation and delivery of care for patients, clinicians and policy makers. ISRCTN: ISRCTN41137900.


Asunto(s)
Análisis por Conglomerados , Servicios Comunitarios de Salud Mental , Prestación Integrada de Atención de Salud , Estado de Salud , Trastornos Mentales/enfermería , Enfermería Psiquiátrica , Proyectos de Investigación , Trastorno Bipolar/enfermería , Servicios Comunitarios de Salud Mental/economía , Comorbilidad , Análisis Costo-Beneficio , Prestación Integrada de Atención de Salud/economía , Inglaterra , Costos de la Atención en Salud , Investigación sobre Servicios de Salud , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/economía , Trastornos Mentales/terapia , Grupo de Atención al Paciente , Enfermería Psiquiátrica/economía , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/enfermería , Calidad de Vida , Esquizofrenia/enfermería , Índice de Severidad de la Enfermedad , Método Simple Ciego , Medicina Estatal , Factores de Tiempo , Resultado del Tratamiento
15.
Biochemistry ; 50(12): 2249-63, 2011 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-21329368

RESUMEN

Apolipoprotein (apo) A-I-containing lipoproteins in the form of high-density lipoproteins (HDL) are inversely correlated with atherosclerosis. Because HDL is a soft form of condensed matter easily deformable by thermal fluctuations, the molecular mechanisms for HDL remodeling are not well understood. A promising approach to understanding HDL structure and dynamics is molecular dynamics (MD). In the present study, two computational strategies, MD simulated annealing (MDSA) and MD temperature jump, were combined with experimental particle reconstitution to explore molecular mechanisms for phospholipid- (PL-) rich HDL particle remodeling. The N-terminal domains of full-length apoA-I were shown to be "sticky", acting as a molecular latch largely driven by salt bridges, until, at a critical threshold of particle size, the associated domains released to expose extensive hydrocarbon regions of the PL to solvent. The "sticky" N-termini also associate with other apoA-I domains, perhaps being involved in N-terminal loops suggested by other laboratories. Alternatively, the overlapping helix 10 C-terminal domains of apoA-I were observed to be extremely mobile or "promiscuous", transiently exposing limited hydrocarbon regions of PL. Based upon these models and reconstitution studies, we propose that separation of the N-terminal domains, as particles exceed a critical size, triggers fusion between particles or between particles and membranes, while the C-terminal domains of apoA-I drive the exchange of polar lipids down concentration gradients between particles. This hypothesis has significant biological relevance since lipid exchange and particle remodeling are critically important processes during metabolism of HDL particles at every step in the antiatherogenic process of reverse cholesterol transport.


Asunto(s)
Apolipoproteína A-I/química , Apolipoproteína A-I/metabolismo , Simulación por Computador , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Simulación de Dinámica Molecular , Secuencia de Aminoácidos , Colesterol/química , Colesterol/metabolismo , Humanos , Fusión de Membrana , Datos de Secuencia Molecular , Tamaño de la Partícula , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Temperatura
17.
J Affect Disord ; 100 Suppl 1: S5-14, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17391773

RESUMEN

OBJECTIVE: An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine's antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms. METHODS: Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed. RESULTS: Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy. The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP. CONCLUSIONS: Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.


Asunto(s)
Antimaníacos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Dibenzotiazepinas/uso terapéutico , Enfermedad Aguda , Antimaníacos/efectos adversos , Antipsicóticos/efectos adversos , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Dibenzotiazepinas/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Humanos , Compuestos de Litio/efectos adversos , Compuestos de Litio/uso terapéutico , Escalas de Valoración Psiquiátrica , Fumarato de Quetiapina , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico
18.
Biophys J ; 88(4): 2789-800, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15653747

RESUMEN

Apolipoprotein B (apoB) is the major protein component of large lipoprotein particles that transport lipids and cholesterol. We have developed a detailed model of the first 1000 residues of apoB using standard sequence alignment programs (ClustalW and MACAW) and the MODELLER6 package for three-dimensional homology modeling. The validity of the apoB model was supported by conservation of disulfide bonds, location of all proline residues in turns and loops, and conservation of the hydrophobic faces of the two C-terminal amphipathic beta-sheets, betaA (residues 600-763) and betaB (residues 780-1000). This model suggests a lipid-pocket mechanism for initiation of lipoprotein particle assembly. In a previous model we suggested that microsomal triglyceride transfer protein might play a structural role in completion of the lipid pocket. We no longer think this likely, but instead propose a hairpin-bridge mechanism for lipid pocket completion. Salt-bridges between four tandem charged residues (717-720) in the turn of the hairpin-bridge and four tandem complementary residues (997-1000) at the C-terminus of the model lock the bridge in the closed position, enabling the deposition of an asymmetric bilayer within the lipid pocket.


Asunto(s)
Apolipoproteínas B/química , Biofisica/métodos , Lipoproteínas/química , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/química , Pollos , Colesterol/química , Biología Computacional/métodos , Cisteína/química , Bases de Datos de Proteínas , Disulfuros/química , Fundulidae , Humanos , Lemur , Membrana Dobles de Lípidos/química , Lípidos/química , Ratones , Modelos Biológicos , Modelos Moleculares , Datos de Secuencia Molecular , Prolina/química , Conformación Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Conejos , Ranidae , Sales (Química)/farmacología , Homología de Secuencia de Aminoácido , Programas Informáticos , Tilapia/metabolismo , Trucha
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