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1.
Diabet Med ; 40(8): e15088, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36929728

RESUMEN

Older adults with diabetes may carry a substantial health burden in Western ageing societies, occupy more than one in four beds in care homes, and are a highly vulnerable group who often require complex nursing and medical care. The global pandemic (COVID-19) had its epicentre in care homes and revealed many shortfalls in diabetes care resulting in hospital admissions and considerable mortality and comorbid illness. The purpose of this work was to develop a national Strategic Document of Diabetes Care for Care Homes which would bring about worthwhile, sustainable and effective quality diabetes care improvements, and address the shortfalls in care provided. A large diverse and multidisciplinary group of stakeholders (NAPCHD) defined 11 areas of interest where recommendations were needed and using a subgroup allocation approach were set tasks to produce a set of primary recommendations. Each subgroup was given 5 starter questions to begin their work and a format to provide responses. During the initial phase, 16 key findings were identified. Overall, after a period of 18 months, 49 primary recommendations were made, and 7 major conclusions were drawn from these. A model of community and integrated diabetes care for care home residents with diabetes was proposed, and a series of 5 'quick-wins' were created to begin implementation of some of the recommendations that would not require significant funding. The work of the NAPCHD is ongoing but we hope that this current resource will help leaders to make these required changes happen.


Asunto(s)
COVID-19 , Diabetes Mellitus , Humanos , Anciano , COVID-19/epidemiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Envejecimiento , Comorbilidad
2.
Ultrasound Obstet Gynecol ; 54(3): 367-375, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30338593

RESUMEN

OBJECTIVE: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. METHODS: This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10th , < 5th and < 3rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at ∼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed. RESULTS: The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10th centile, 68% for < 5th centile and 89% for < 3rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10th centile with an OR of 9.1, < 5th centile with an OR of 17.3 and < 3rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone. CONCLUSIONS: In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
Retardo del Crecimiento Fetal/diagnóstico por imagen , Arteria Cerebral Media/fisiopatología , Insuficiencia Placentaria/fisiopatología , Ultrasonografía Prenatal , Arteria Uterina/fisiopatología , Adulto , Biometría , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Edad Gestacional , Humanos , Arteria Cerebral Media/diagnóstico por imagen , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Valores de Referencia , Arteria Uterina/diagnóstico por imagen
3.
Bull Math Biol ; 78(3): 436-67, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26934886

RESUMEN

The earliest cell fate decisions in a developing embryo are those associated with establishing the germ layers. The specification of the mesoderm and endoderm is of particular interest as the mesoderm is induced from the endoderm, potentially from an underlying bipotential group of cells, the mesendoderm. Mesendoderm formation has been well studied in an amphibian model frog, Xenopus laevis, and its formation is driven by a gene regulatory network (GRN) induced by maternal factors deposited in the egg. We have recently demonstrated that the axolotl, a urodele amphibian, utilises a different topology in its GRN to specify the mesendoderm. In this paper, we develop spatially structured mathematical models of the GRNs governing mesendoderm formation in a line of cells. We explore several versions of the model of mesendoderm formation in both Xenopus and the axolotl, incorporating the key differences between these two systems. Model simulations are able to reproduce known experimental data, such as Nodal expression domains in Xenopus, and also make predictions about how the positional information derived from maternal factors may be interpreted to drive cell fate decisions. We find that whilst cell-cell signalling plays a minor role in Xenopus, it is crucial for correct patterning domains in axolotl.


Asunto(s)
Anfibios/embriología , Modelos Biológicos , Ambystoma mexicanum/embriología , Ambystoma mexicanum/genética , Proteínas Anfibias/genética , Anfibios/genética , Animales , Simulación por Computador , Endodermo/embriología , Regulación del Desarrollo de la Expresión Génica , Redes Reguladoras de Genes , Conceptos Matemáticos , Mesodermo/embriología , Ligandos de Señalización Nodal/genética , Xenopus laevis/embriología , Xenopus laevis/genética
4.
Spinal Cord ; 54(9): 675-81, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26666508

RESUMEN

STUDY DESIGN: Single group, pretest-post-test study. OBJECTIVES: To determine the effects of a non-task-specific, voluntary, progressive aerobic exercise training (AET) intervention on fitness and walking-related outcomes in ambulatory adults with chronic motor-incomplete SCI. SETTING: Rehabilitation research center. METHODS: Ten ambulatory individuals (50% female; 57.94±9.33 years old; 11.11±9.66 years postinjury) completed voluntary, progressive moderate-to-vigorous intensity AET on a recumbent stepper 3 days per week for 6 weeks. The primary outcome measures were aerobic capacity (VO2peak (volume of oxygen that the body can use during physical exertion)) and self-selected overground walking speed (OGWS). Secondary outcome measures included walking economy, 6-minute walk test (6MWT), daily step counts, Walking Index for Spinal Cord Injury (WISCI-II), Dynamic Gait Index (DGI) and Berg Balance Scale (BBS). RESULTS: Nine participants completed all testing and training. Significant improvements in aerobic capacity (P=0.011), OGWS (P=0.023), the percentage of VO2peak used while walking at self-selected speed (P=0.03) and daily step counts (P=0.025) resulted following training. CONCLUSIONS: The results indicate that total-body, voluntary, progressive AET is safe, feasible, and effective for improving aerobic capacity, walking speed, and select walking-related outcomes in an exclusively ambulatory SCI sample. This study suggests the potential for non-task-specific aerobic exercise to improve walking following incomplete SCI and builds a foundation for further investigation aimed at the development of exercise based rehabilitation strategies to target functionally limiting impairments in ambulatory individuals with chronic SCI.


Asunto(s)
Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Adolescente , Adulto , Anciano , Enfermedad Crónica , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Centros de Rehabilitación , Traumatismos de la Médula Espinal/rehabilitación , Estadísticas no Paramétricas , Índices de Gravedad del Trauma , Resultado del Tratamiento , Caminata , Adulto Joven
5.
Int J Dent Hyg ; 14(3): 209-14, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26198308

RESUMEN

OBJECTIVES: Sodium bicarbonate has been shown clinically to be efficacious at removing dental plaque; however, its effect of mechanism against biofilms has not been evaluated in vitro. Here, we used a well-established in vitro plaque biofilm model to investigate the disruption of dental plaque biofilms. METHODS: Biofilms were grown in a constant depth film fermentor for up to 14 days. The fermentor was inoculated with pooled human saliva and growth maintained with artificial saliva. After various time points, replicate biofilms were removed and subjected to treatment at varying concentrations of sodium bicarbonate. Disruption of the plaque was assessed by viable counts and microscopy. RESULTS: The viable count results showed that younger biofilms were less susceptible to the action of sodium bicarbonate; however, biofilms of 7 days and older were increasingly susceptible to the material with the oldest biofilms being the most susceptible. Sixty-seven percentage of sodium bicarbonate slurry was able to reduce the number of organisms present by approx. 3 log10 . These quantitative data were corroborated qualitatively with both confocal and electron microscopy, which both showed substantial qualitative removal of mature biofilms. CONCLUSIONS: The results from this study have shown that sodium bicarbonate is able to disrupt mature dental plaque grown in vitro and that its reported efficacy in maintaining oral hygiene may be related to this key factor.


Asunto(s)
Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Placa Dental/tratamiento farmacológico , Bicarbonato de Sodio/farmacología , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Reactores Biológicos , Recuento de Colonia Microbiana , Placa Dental/microbiología , Microscopía Confocal , Microscopía Electrónica , Higiene Bucal , Saliva , Saliva Artificial , Bicarbonato de Sodio/administración & dosificación , Factores de Tiempo
6.
HIV Med ; 15(3): 182-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24025108

RESUMEN

OBJECTIVES: This was a cross-sectional study with a nested case-control analysis among a cohort of HIV-infected adults aiming to explore the prevalence of and risk factors for elective hip surgery (total hip arthroplasty and resurfacing). METHODS: Cases were identified from the out-patient database of HIV-infected adults attending one tertiary hospital service. For each case, five controls from the same database matched by age, gender and ethnicity were identified. From the case notes, information about demographic factors, HIV factors and risk factors for hip surgery attributable to osteoarthritis or avascular necrosis (body mass index, lipids, alcohol, comorbidities and treatment with oral glucocorticoids) was extracted. RESULTS: Among the cohort of 1900 HIV-infected out-patients, 13 cases (12 male) who had undergone hip surgery [0.7%; 95% confidence interval (CI) 0.3-1.1%] were identified, with a median age of 47 years. Eleven of the 13 cases (85%) were Caucasian and seven of the 13 were in stage 3 of HIV infection. Fewer of the cases were in the asymptomatic stage of infection compared with controls [odds ratio (OR) for stage 2 or 3 infection 4.0; 95% CI 0.8-18.5]. Ever having used oral glucocorticoids was highly significantly associated with elective hip surgery (OR 44.6; 95% CI 5.7-347.7). CONCLUSIONS: Among this young cohort, the prevalence of elective hip surgery was 0.7%, with the median age at surgery being 47 years. Ever having been exposed to systemic glucocorticoids was highly significantly associated with elective hip surgery, suggesting that the principal mechanism underlying the need for surgery was avascular necrosis. There may be an increased need for elective hip surgery associated with HIV infection.


Asunto(s)
Glucocorticoides/efectos adversos , Infecciones por VIH/complicaciones , Osteoartritis de la Cadera/etiología , Osteonecrosis/etiología , Adulto , Artroplastia de Reemplazo de Cadera , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Glucocorticoides/uso terapéutico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/cirugía , Osteonecrosis/epidemiología , Osteonecrosis/cirugía , Factores de Riesgo
7.
Soc Sci Res ; 44: 211-23, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24468445

RESUMEN

How can a researcher engage a participant in a survey, when the subject matter may be perceived as 'challenging' or even be totally unfamiliar to the participant? The Genomethics study addressed this via the creation and delivery of a novel online questionnaire containing 10 integrated films. The films documented various ethical dilemmas raised by genomic technologies and the survey ascertained attitudes towards these. Participants were recruited into the research using social media, traditional media and email invitation. The film-survey strategy was successful: 11,336 initial hits on the survey website led to 6944 completed surveys. Participants included from those who knew nothing of the subject matter through to experts in the field of genomics (61% compliance rate), 72% of participants answered every single question. This paper summarises the survey design process and validation methods applied. The recruitment strategy and results from the survey are presented elsewhere.


Asunto(s)
Actitud , Confidencialidad , Privacidad Genética , Genoma , Genómica/ética , Películas Cinematográficas , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ética , Femenino , Humanos , Internet , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto Joven
8.
J Math Biol ; 67(6-7): 1393-424, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23070212

RESUMEN

Nodal signals are key regulators of mesoderm and endoderm development in vertebrate embryos. It has been observed experimentally that in Xenopus embryos the spatial range of Nodal signals is restricted by the signal Antivin (also known as Lefty). Nodal signals can activate both Nodal and Antivin, whereas Antivin is thought to antagonise Nodal by binding either directly to it or to its receptor. In this paper we develop a mathematical model of this signalling network in a line of cells. We consider the heterodimer and receptor-mediated inhibition mechanisms separately and find that, in both cases, the restriction by Antivin to the range of Nodal signals corresponds to wave pinning in the model. Our analysis indicates that, provided Antivin diffuses faster than Nodal, either mechanism can robustly account for the experimental data. We argue that, in the case of Xenopus development, it is wave pinning, rather than Turing-type patterning, that is underlying Nodal-Antivin dynamics. This leads to several experimentally testable predictions, which are discussed. Furthermore, for heterodimer-mediated inhibition to prevent waves of Nodal expression from propagating, the Nodal-Antivin complex must be turned over, and diffusivity of the complex must be negligible. In the absence of molecular mechanisms regulating these, we suggest that Antivin restricts Nodal signals via receptor-mediated, and not heterodimer-mediated, inhibition.


Asunto(s)
Factores de Determinación Derecha-Izquierda/fisiología , Mesodermo/embriología , Modelos Biológicos , Proteína Nodal/fisiología , Transducción de Señal/fisiología , Xenopus/embriología , Animales , Redes Reguladoras de Genes/fisiología , Factores de Determinación Derecha-Izquierda/genética , Proteína Nodal/genética , Transducción de Señal/genética
9.
J Intellect Disabil Res ; 57(5): 393-408, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22458301

RESUMEN

BACKGROUND: The behavioural determinants of health among people with mild/moderate intellectual disabilities (ID) are of increasing concern. With the closure of long-stay institutions, more people with ID are living in the community. As they lead more ordinary and less restricted lives, people with ID may be exposed to social and environmental pressures that encourage them to adopt behaviours that impact negatively on their health. Levels of smoking and alcohol consumption in this client group are of particular concern. METHODS: We undertook a mixed method review of the literature, aiming to assess the Feasibility, Appropriateness, Meaningfulness and Effectiveness (FAME) of interventions designed to address the use of tobacco and/or alcohol in people with mild/moderate ID. Key electronic databases were searched (e.g., Medline, Cochrane Register of Controlled Trials, PsycINFO) from 1996 to 2011. The search was developed using appropriate subject headings and key words (e.g., intellectual disability, tobacco use, alcohol drinking, health promotion). On completion of the database searches, inclusion/exclusion criteria, based on an adaptation of the PICO framework (Population, Intervention, Comparison, Outcomes), were applied. Methodological quality was assessed using a seven-point rating scale. RESULTS: Database searches identified 501 unique records, of which nine satisfied the inclusion criteria. Four focused on tobacco, three on alcohol and two on both tobacco and alcohol. Located in the U.K., the U.S.A. and Australia, the studies aimed to increase knowledge levels and/or change behaviour (e.g., to encourage smoking cessation). One was a randomised controlled trial, one a quasi-experiment and the others were before and after studies and/or case studies. Methodological quality was poor or moderate. The combined studies had a sample size of 341, with ages ranging from 14 to 54 years. The interventions were delivered by professionals (e.g., in health, social care, education) during sessions that spanned a period of three weeks to one academic year. The studies highlighted a number of important issues linked to the appropriateness of interventions for this client group (e.g., use of pictures, quizzes, role play, incentives); however, in the majority of cases the interventions appeared to lack a theoretical framework (e.g., behaviour change theory). The appropriateness of the outcome measures for use with this client group was not tested. One study discussed feasibility (teachers delivering lessons on alcohol and tobacco) and only one was informative in terms of effectiveness, i.e., increasing knowledge of the health and social dangers of smoking and excessive alcohol consumption. CONCLUSIONS: This review is the first to systematically collate evidence on tobacco and alcohol-related interventions for people with ID. While there is currently little evidence to guide practice, the review delivers clear insights for the development of interventions and presents a strong case for more robust research methods. In particular there is a need to test the effectiveness of interventions in large-scale, well-designed trials and to ensure that outcome measures are developed/tailored appropriately for this client group.


Asunto(s)
Consumo de Bebidas Alcohólicas/terapia , Promoción de la Salud/métodos , Discapacidad Intelectual/complicaciones , Fumar/terapia , Cese del Uso de Tabaco/métodos , Humanos
10.
Phys Rev Lett ; 107(4): 047203, 2011 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-21867036

RESUMEN

Scaling arguments and precise simulations are used to study the square lattice ±J Ising spin glass, a prototypical model for glassy systems. Droplet theory explains, and our numerical results show, entropically stabilized long-range spin-glass order at zero temperature, which resembles the energetic stabilization of long-range order in higher-dimensional models at finite temperature. At low temperature, a temperature-dependent crossover length scale is used to predict the power-law dependence on temperature of the heat capacity and clarify the importance of disorder distributions.

11.
Ecol Appl ; 20(1): 278-88, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20349847

RESUMEN

While many wildlife species are threatened, some populations have recovered from previous overexploitation, and data linking these population increases with disease dynamics are limited. We present data suggesting that free-ranging elk (Cervus elaphus) are a maintenance host for Brucella abortus in new areas of the Greater Yellowstone Ecosystem (GYE). Brucellosis seroprevalence in free-ranging elk increased from 0-7% in 1991-1992 to 8-20% in 2006-2007 in four of six herd units around the GYE. These levels of brucellosis are comparable to some herd units where elk are artificially aggregated on supplemental feeding grounds. There are several possible mechanisms for this increase that we evaluated using statistical and population modeling approaches. Simulations of an age-structured population model suggest that the observed levels of seroprevalence are unlikely to be sustained by dispersal from supplemental feeding areas with relatively high seroprevalence or an older age structure. Increases in brucellosis seroprevalence and the total elk population size in areas with feeding grounds have not been statistically detectable. Meanwhile, the rate of seroprevalence increase outside the feeding grounds was related to the population size and density of each herd unit. Therefore, the data suggest that enhanced elk-to-elk transmission in free-ranging populations may be occurring due to larger winter elk aggregations. Elk populations inside and outside of the GYE that traditionally did not maintain brucellosis may now be at risk due to recent population increases. In particular, some neighboring populations of Montana elk were 5-9 times larger in 2007 than in the 1970s, with some aggregations comparable to the Wyoming feeding-ground populations. Addressing the unintended consequences of these increasing populations is complicated by limited hunter access to private lands, which places many ungulate populations out of administrative control. Agency-landowner hunting access partnerships and the protection of large predators are two management strategies that may be used to target high ungulate densities in private refuges and reduce the current and future burden of disease.


Asunto(s)
Brucelosis/veterinaria , Ciervos , Animales , Brucelosis/epidemiología , Simulación por Computador , Ecosistema , Modelos Biológicos , Montana/epidemiología , Densidad de Población , Wyoming/epidemiología
12.
Bull Math Biol ; 72(6): 1383-407, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20135237

RESUMEN

The hormone auxin is implicated in regulating a diverse range of developmental processes in plants. Auxin acts in part by inducing the Aux/IAA genes. The associated pathway comprises multiple negative feedback loops (whereby Aux/IAA proteins can repress Aux/IAA genes) that are disrupted by auxin mediating the turnover of Aux/IAA protein. In this paper, we develop a mathematical model of a single Aux/IAA negative feedback loop in a population of identical cells. The model has a single steady-state. We explore parameter space to uncover a number of dynamical regimes. In particular, we identify the ratio between the Aux/IAA protein and mRNA turnover rates as a key parameter in the model. When this ratio is sufficiently small, the system can evolve to a stable limit cycle, corresponding to an oscillation in Aux/IAA expression levels. Otherwise, the steady-state is either a stable-node or a stable-spiral. These observations may shed light on recent experimental results.


Asunto(s)
Arabidopsis/crecimiento & desarrollo , Retroalimentación Fisiológica , Ácidos Indolacéticos/metabolismo , Modelos Biológicos , Reguladores del Crecimiento de las Plantas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas
13.
Int J Clin Pract ; 64(8): 1121-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20236369

RESUMEN

Hypoglycaemia and its consequences represent a significant risk for many people who have type 2 diabetes, and hypoglycaemia is currently under-recognised and commonly avoidable. Current clinical guidelines recommend the targeting of tight glycaemic control and this strategy may also be associated with an increased risk of hypoglycaemia. Hypoglycaemia impacts on morbidity, mortality and quality of life of people with type 2 diabetes, and improved recognition of the symptoms of hypoglycaemia will allow effective treatment and reduce the risk of progression to more severe episodes. A common cause of hypoglycaemia in people with type 2 diabetes is glucose-lowering medication, in particular, those which raise insulin independently of ambient glucose concentration such as sulphonylureas and exogenous insulin. The recently published National Institute for Health and Clinical Excellence guideline recommends the use of Dipeptidyl peptidase-4 inhibitors or thiazolidinediones (glitazones) as alternative second-line therapy instead of a sulphonylurea in those patients who are at significant risk of hypoglycaemia and its consequences.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Factores de Edad , Consumo de Bebidas Alcohólicas/efectos adversos , Costo de Enfermedad , Diabetes Mellitus Tipo 2/economía , Angiopatías Diabéticas/etiología , Miedo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/diagnóstico , Guías de Práctica Clínica como Asunto , Calidad de Vida , Factores de Riesgo , Autocuidado
14.
J Mol Biol ; 432(13): 3790-3801, 2020 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-32416094

RESUMEN

RNF12 is a widely expressed ubiquitin E3 ligase that is required for X-chromosome inactivation, regulation of LIM-domain containing transcription factors, and TGF-ß signaling. A RING domain at the C terminus of RNF12 is important for its E3 ligase activity, and mutations in the RING domain are associated with X-linked intellectual disability. Here we have characterized ubiquitin transfer by RNF12, and show that the RING domain can bind to, and is active with, ubiquitin conjugating enzymes (E2s) that produce degradative ubiquitin chains. We report the crystal structures of RNF12 in complex with two of these E2 enzymes, as well as with an E2~Ub conjugate in a closed conformation. These structures form a basis for understanding the deleterious effect of a number of disease causing mutations. Comparison of the RNF12 structure with other monomeric RINGs suggests that a loop prior to the core RING domain has a conserved and essential role in stabilization of the active conformation of the bound E2~Ub conjugate. Together these findings provide a framework for better understanding substrate ubiquitylation by RNF12 and the impact of disease causing mutations.


Asunto(s)
Discapacidad Intelectual/genética , Conformación Proteica , Ubiquitina-Proteína Ligasas/genética , Ubiquitina/genética , Cristalografía por Rayos X , Humanos , Discapacidad Intelectual/patología , Dominios Proteicos/genética , Proteolisis , Enzimas Ubiquitina-Conjugadoras/genética , Ubiquitina-Proteína Ligasas/ultraestructura , Ubiquitinación/genética , Inactivación del Cromosoma X/genética
15.
J Theor Biol ; 260(1): 41-55, 2009 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-19490918

RESUMEN

In this paper we develop a model of mesendoderm specification in Xenopus laevis based on an existing gene regulation network. The mesendoderm is a population of cells that may contribute to either the mesoderm or endoderm. The model that we develop encompasses the time evolution of transcription factor concentrations in a single cell and is shown to have stable steady states that correspond to mesoderm and anterior mesendodermal cell types, but not endoderm (except in cells where Goosecoid expression is inhibited). Both in vitro and in vivo versions of the model are developed and analysed, the former indicating how cell fate is determined in large part by the concentration of Activin administered to a cell, with the model results comparing favourably with current quantitative experimental data. A numerical investigation of the in vivo model suggests that cell fate is determined largely by a VegT and beta-Catenin pre-pattern, subsequently being reinforced by Nodal. We argue that this sensitivity of the model to a VegT and beta-Catenin pre-pattern indicates that a key VegT self-limiting mechanism (for which there is experimental evidence) is absent from the model. Furthermore, we find that the lack of a steady state corresponding to endoderm is entirely consistent with current in vivo data, and that the in vivo model corresponds to mesendoderm specification on the dorsal, but not the ventral, side of the embryo.


Asunto(s)
Tipificación del Cuerpo/fisiología , Endodermo/citología , Mesodermo/citología , Modelos Biológicos , Xenopus laevis/embriología , Animales , Tipificación del Cuerpo/genética , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Embrión no Mamífero/fisiología , Desarrollo Embrionario/genética , Desarrollo Embrionario/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiología , Factores de Transcripción/metabolismo , Xenopus laevis/genética , Xenopus laevis/fisiología
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 79(5 Pt 1): 050101, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19518396

RESUMEN

We study the minimum-energy configuration of a d -dimensional elastic interface in a random potential tied to a harmonic spring. As a function of the spring position, the center of mass of the interface changes in discrete jumps, also called shocks or "static avalanches." We obtain analytically the distribution of avalanche sizes and its cumulants within an =4-d expansion from a tree and one-loop resummation using functional renormalization. This is compared with exact numerical minimizations of interface energies for random-field disorder in d=2,3 . Connections to dynamic avalanches are mentioned.

17.
Lett Appl Microbiol ; 48(4): 472-7, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19228292

RESUMEN

AIM: To determine the effect of the surface roughness of denture acrylic on the attachment of Streptococcus oralis. METHODS AND RESULTS: Roughened denture acrylic samples were assessed for bacterial attachment, over time, using microscopy. The area of the image covered by bacteria was calculated and converted into a percentage of the total area sampled. The results showed an increasing bacterial coverage with time of incubation and increasing roughness. Differences were seen between heat cured acrylic and cold cured acrylic. CONCLUSION: This study successfully demonstrated a system for the assessment of the amount of attached bacteria on denture acrylic varying roughness. The system was able to discern the difference in surface area coverage by attached bacteria over a roughness range relevant to brushing dentures with dentifrices. SIGNIFICANCE AND IMPACT OF STUDY: This study provides strong support for the scratches caused by brushing dentures with dentifrice encouraging bacterial attachment. This is likely to have a significant effect on efficacy of denture cleaning, general hygiene and biofilm re-formation between cleaning regimens and may indicate that alternative low abrasive cleaners, such as antimicrobial denture-cleaning tablets, offer a more appropriate regimen.


Asunto(s)
Resinas Acrílicas/química , Adhesión Bacteriana , Dentaduras , Streptococcus oralis/fisiología , Frío , Recuento de Colonia Microbiana , Dentífricos , Calor , Humanos , Propiedades de Superficie , Cepillado Dental , Pastas de Dientes
18.
JBJS Case Connect ; 9(4): e0141, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31850961

RESUMEN

CASES: We present 2 cases of traumatic testicular dislocation associated with a pelvic ring injury after a motorcycle collision. Case 1 describes bilateral testicular dislocation discovered intraoperatively. Urology was consulted, and the testicles were manually reduced under general anesthesia. Case 2 describes unilateral testicular dislocation discovered at the 1-month follow-up after pelvic ring fixation. Concern for infarction prompted urology to take the patient for surgical reduction. Both cases resolved uneventfully without genitourinary complaints at the follow-up. CONCLUSIONS: Testicular dislocation is rare but should be considered in the setting of pelvic injury due to a motorcycle collision. Detection warrants urgent urologic consultation.


Asunto(s)
Pelvis , Testículo , Accidentes de Tránsito , Humanos , Masculino , Persona de Mediana Edad , Motocicletas , Pelvis/diagnóstico por imagen , Pelvis/lesiones , Pelvis/cirugía , Testículo/diagnóstico por imagen , Testículo/lesiones , Testículo/patología , Testículo/cirugía
19.
Curr Med Res Opin ; 22(6): 1181-91, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16846551

RESUMEN

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.


Asunto(s)
LDL-Colesterol/sangre , Fluorobencenos/administración & dosificación , Guías como Asunto , Ácidos Heptanoicos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Sulfonamidas/administración & dosificación , Anciano , Atorvastatina , Europa (Continente) , Femenino , Humanos , Estudios Longitudinales , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Rosuvastatina Cálcica , Cambio Social
20.
J Orthop Surg (Hong Kong) ; 14(1): 13-6, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16598080

RESUMEN

PURPOSE: To assess the prevalence of proximal high-origin anterior tibial artery and its surgical significance. METHODS: 100 knees were prospectively studied using colour Doppler ultrasonography. No patient had a history of lower-limb arterial pathology or previous knee surgery. All ultrasound images were assessed by a single experienced vascular technician to eliminate inter-observer variability. RESULTS: The mean age of the patients was 56 years (range, 21-96 years). Prevalence of the high-origin anterior tibial arterial pattern was 6%, greater than that reported by previous angiographic or cadaveric studies. In all patients with high-origin anterior tibial artery, the artery was in direct contact with the posterior cortex of the tibia. CONCLUSION: This highlights the danger of using sharp instruments in knee procedures that involve extension of osteotomy to the posterior tibial cortex, particularly high-tibial osteotomy and total knee replacement. Knowledge of the anatomical variations in the branching of the popliteal artery is important because damage to its branches can be limb- or life-threatening.


Asunto(s)
Articulación de la Rodilla/cirugía , Arterias Tibiales/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Poplítea/anatomía & histología , Arteria Poplítea/diagnóstico por imagen , Arterias Tibiales/anomalías , Arterias Tibiales/diagnóstico por imagen , Ultrasonografía Doppler en Color
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