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1.
Front Public Health ; 11: 1227075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522007

RESUMO

Background: Adolescence is recognised as a period of nutritional vulnerability, with evidence indicating that United Kingdom adolescents have suboptimal dietary intakes with many failing to meet dietary recommendations. Additionally, adolescence is a time of transition when they become more independent in their dietary choices and begin to develop their own sense of autonomy and are less reliant on their parent's guidance, which is reported to lead to less favourable dietary behaviours. Reducing the prevalence of poor dietary intakes and the associated negative health consequences among this population is a public health priority and schools represent an important setting to promote positive dietary behaviours. The aim of this school-based study was to explore the factors and barriers which influence food choices within the school canteen and to identify feasible strategies to promote positive dietary behaviours within this setting. Methods: Thirteen focus groups with 86 pupils in Year 8 (n = 37; aged 11-12 years) and Year 9 (n = 49; aged 12-13 years) in six secondary schools across Northern Ireland, United Kingdom were conducted. Additionally, one-to-one virtual interviews were conducted with 29 school staff [principals/vice-principals (n = 4); teachers (n = 17); and caterers (n = 7)] across 17 secondary schools and an Education Authority (EA) senior staff member (n = 1). Focus groups and interviews were audio-recorded, transcribed, and analysed following an inductive thematic approach. Results: Using the ecological framework, multiple factors were identified which influenced pupils' selection of food in the school canteen at the individual (e.g., time/convenience), social (e.g., peer influence), physical (e.g., food/beverage placement), and macro environment (e.g., food provision) level. Suggestions for improvement of food choices were also identified at each ecological level: individual (e.g., rewards), social (e.g., pupil-led initiatives), physical (e.g., labelling), and macro environment (e.g., whole-school approaches). Conclusion: Low-cost and non-labour intensive practical strategies could be employed, including menu and labelling strategies, placement of foods, reviewing pricing policies and whole-school initiatives in developing future dietary interventions to positively enhance adolescents' food choices in secondary schools.


Assuntos
Dieta , Instituições Acadêmicas , Adolescente , Humanos , Escolaridade , Pesquisa Qualitativa , Grupos Focais
2.
iScience ; 26(4): 106489, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37096039

RESUMO

Space-based remote sensing can make an important contribution toward monitoring greenhouse gas emissions and removals from the agriculture, forestry, and other land use (AFOLU) sector, and to understanding and addressing human-caused climate change through the UNFCCC Paris Agreement. Space agencies have begun to coordinate their efforts to identify needs, collect and harmonize available data and efforts, and plan and maintain a long-term roadmap for observations. International cooperation is crucial in developing and realizing the roadmap, and the Committee on Earth Observation Satellites (CEOS) is a key coordinating driver of this effort. Here, we first identify the data and information that will be useful to support the global stocktake (GST) of the Paris Agreement. Then, the paper explains how existing and planned space-based capabilities and products can be used and combined, particularly in the land use sector, and provides a workflow for their harmonization and contribution to greenhouse gas inventories and assessments at the national and global level.

3.
Virol J ; 19(1): 202, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457114

RESUMO

BACKGROUND: The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE). METHODS: Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability. RESULTS: Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high. CONCLUSIONS: Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudantes , Testes Imunológicos , Soroconversão
4.
Br J Psychother ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36246549

RESUMO

The Covid-19 pandemic brought a heightened fear of death and illness, and increased experiences of isolation, loneliness and aloneness. In this article we describe clinical experiences of psychotherapists in Argentina, the UK and Germany in order to explore how the impacts of the pandemic are variously felt and mediated by inner resources. We explore the capacity to relate internally to good experiences of infancy and a secure internal world, and the risks of loneliness, and interpersonal and intrapsychic withdrawal, that lead to vulnerability in patients and therapists. We contrast instances where psychotherapy in response to increased fears of death, infection and isolation is facilitative of change and growth, with situations where perverse, destructive or defensive relating predominate. We ask if we are witnessing and, through our therapeutic activities, contributing to the emergence of new ways of understanding the internal conflicts of this Covid-19 age, and tentatively identify some key emerging themes; the capacity for facilitative interactions and change; identifications with the powerful virus; an increase in paranoid anxieties and the potential for a more considerate, 'care-full' way of relating.

5.
Int J Psychoanal ; 103(1): 71-88, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35168484

RESUMO

The legalisation of assisted dying, including euthanasia and physician assisted suicide, is increasing in countries across the world and constitutes a key contemporary debate, reflecting social changes, in which two views of suicide conflict; that (1) rational reasons justify assisted suicide, providing dignity and control of terminal illness and (2) suicidal wishes are driven by unconscious and disturbing internal conflicts. In this paper we explore the unconscious motives and meanings of requests for assisted suicide. Although there is a paucity of psychoanalytic literature on the subject, and an absence of practice examples, we make two links, firstly, with the literature of palliative and end of life care, and, secondly, with psychoanalytic understanding of suicide, in order to develop the view that unconscious factors are crucial to understanding requests for assisted suicide. We provide an illustrative case example of psychodynamic psychotherapy with a 94-year-old woman, drawing out theoretical and practice implications. We show that unconscious factors and motives lie behind apparently rational requests for assisted suicide, and attention to these through psychoanalytically informed treatment can bring about therapeutic change.


Assuntos
Eutanásia , Psicoterapia Psicodinâmica , Suicídio Assistido , Idoso de 80 Anos ou mais , Feminino , Humanos , Cuidados Paliativos
6.
Emerg Infect Dis ; 27(10): 2662-2665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34399086

RESUMO

We used the BinaxNOW COVID-19 Ag Card to screen 1,540 asymptomatic college students for severe acute respiratory syndrome coronavirus 2 in a low-prevalence setting. Compared with reverse transcription PCR, BinaxNOW showed 20% overall sensitivity; among participants with culturable virus, sensitivity was 60%. BinaxNOW provides point-of-care screening but misses many infections.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Estudantes
7.
Epilepsia ; 62(8): 1985-1999, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34212374

RESUMO

OBJECTIVE: Infantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats. METHODS: Spasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult mice, video-EEG (electroencephalography) scoring for seizures and sleep and histology were done blinded to treatment. RESULTS: Motor-type seizures developed in 66.7% of multiple-hit rats, usually from sleep, but were reduced in the pulse-rapamycin-treated group (20%, p = .043 vs multiple-hit) and rare in other groups (0-9.1%, p < .05 vs multiple-hit). Spike-and-wave bursts had a slower frequency in multiple-hit rats (5.4-5.8Hz) than in the other groups (7.6-8.3Hz) (p < .05); pulse rapamycin had no effect on the hourly spike-and-wave burst rates in adulthood. Rapamycin, however, reduced the time spent in slow-wave-sleep (17.2%), which was increased in multiple-hit rats (71.6%, p = .003). Sham rats spent more time in wakefulness (43.7%) compared to controls (30.6%, p = .043). Multiple-hit rats, with or without rapamycin treatment, had right more than left corticohippocampal, basal ganglia lesions. There was no macroscopic pathology in the other groups. SIGNIFICANCE: Structural corticohippocampal/basal ganglia lesions increase the risk for post-infantile spasms epilepsy, Lennox-Gastaut syndrome features, and sleep dysregulation. Pulse rapamycin treatment for infantile spasms has anti-epileptogenic effects, despite the structural lesions, and decreases the time spent in slow wave sleep.


Assuntos
Epilepsia , Síndrome de Lennox-Gastaut , Espasmo , Animais , Modelos Animais de Doenças , Eletroencefalografia , Masculino , Camundongos , Ratos , Convulsões , Sirolimo
8.
Glob Change Biol Bioenergy ; 12(6): 445-457, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32612682

RESUMO

The application of organic materials to soil can recycle nutrients and increase organic matter in agricultural lands. Digestate can be used as a nutrient source for crop production but it has also been shown to stimulate greenhouse gas (GHG) emissions from amended soils. While edaphic factors, such as soil texture and pH, have been shown to be strong determinants of soil GHG fluxes, the impact of the legacy of previous management practices is less well understood. Here we aim to investigate the impact of such legacy effects and to contrast them against soil properties to identify the key determinants of soil GHG fluxes following digestate application. Soil from an already established field experiment was used to set up a pot experiment, to evaluate N2O, CH4 and CO2 fluxes from cattle-slurry-digestate amended soils. The soil had been treated with farmyard manure, green manure or synthetic N-fertilizer, 18 months before the pot experiment was set up. Following homogenization and a preincubation stage, digestate was added at a concentration of 250 kg total N/ha eq. Soil GHG fluxes were then sampled over a 64 day period. The digestate stimulated emissions of the three GHGs compared to controls. The legacy of previous soil management was found to be a key determinant of CO2 and N2O flux while edaphic variables did not have a significant effect across the range of variables included in this experiment. Conversely, edaphic variables, in particular texture, were the main determinant of CH4 flux from soil following digestate application. Results demonstrate that edaphic factors and current soil management regime alone are not effective predictors of soil GHG flux response following digestate application. Knowledge of the site management in terms of organic amendments is required to make robust predictions of the likely soil GHG flux response following digestate application to soil.

9.
Br J Psychiatry ; 214(6): 320-328, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30816079

RESUMO

BACKGROUND: Preventing suicide and self-harm is a global health priority. Although there is a growing evidence base for the effectiveness of psychoanalytic and psychodynamic psychotherapies for a range of disorders, to date there has been no systematic review of its effectiveness in reducing suicidal and self-harming behaviours.AimsTo systematically review randomised controlled trials of psychoanalytic and psychodynamic psychotherapies for suicidal attempts and self-harm. METHOD: We searched PubMed, PsycINFO, Psycharticles, CINAHL, EMBASE and the Cochrane Central Register of Controlled Trials for randomise controlled trials of psychoanalytic and psychodynamic psychotherapies for reducing suicide attempts and self-harm. RESULTS: Twelve trials (17 articles) were included in the meta-analyses. Psychoanalytic and psychodynamic therapies were effective in reducing the number of patients attempting suicide (pooled odds ratio, 0.469; 95% CI 0.274-0.804). We found some evidence for significantly reduced repetition of self-harm at 6-month but not 12-month follow-up. Significant treatment effects were also found for improvements in psychosocial functioning and reduction in number of hospital admissions. CONCLUSIONS: Psychoanalytic and psychodynamic psychotherapies are indicated to be effective in reducing suicidal behaviour and to have short-term effectiveness in reducing self-harm. They can also be beneficial in improving psychosocial well-being. However, the small number of trials and moderate quality of the evidence means further high-quality trials are needed to confirm our findings and to identity which specific components of the psychotherapies are effective.Declaration of interestNone.


Assuntos
Terapia Psicanalítica/métodos , Psicoterapia Psicodinâmica/métodos , Comportamento Autodestrutivo/prevenção & controle , Tentativa de Suicídio/prevenção & controle , Humanos , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia
10.
Science ; 354(6311): 421-422, 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27789831
11.
Epilepsia ; 55(1): 94-102, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24321005

RESUMO

OBJECTIVE: Infantile spasms (IS) have poor outcomes and limited treatment options, including vigabatrin, a γ-aminobutyric acid (GABA) aminotransferase inactivator. Vigabatrin has been associated with retinal toxicity. A high affinity vigabatrin analogue (CPP-115; Catalyst Pharmaceutical Partners, Inc., Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test the efficacy of CPP-115 in reducing spasms and its tolerability in the multiple-hit rat model of IS, in which daily vigabatrin reduced spasms for only one day, but was not well tolerated. METHODS: Male rats were treated with the protocol of the multiple-hit model of IS on postnatal day 3 (PN3). Using a randomized, blinded, vehicle-controlled, dose-response study design, CPP-115 (0.1, 1, or 5 mg/kg intraperitoneally [i.p.]) or vehicle was given daily (PN4-12) or as a single injection (PN7) after spasm onset. Intermittent video- or video-electroencephalography (EEG) monitoring was done. Secondary end points included the following: daily weights, survival, performance on open field activity, surface righting time, and negative geotaxis (PN3-20), horizontal bar (PN13-20), and Barnes maze (PN16-19). Statistics used a linear mixed model of raw or normalized log-transformed data, taking into account the repeated observations on each animal. RESULTS: The lower CPP-115 doses (0.1-1 mg/kg/day, PN4-12) reduced spasms between PN6 and 7 without increasing mortality. CPP-115 at 5 mg/kg/day (PN4-12) reduced spasms earlier (PN5), but was eventually lethal. A single CPP-115 injection (1 mg/kg, i.p.) decreased electroclinical spasms acutely but transiently. CPP-115 transiently improved the probability to >50% reduction of spasms, but did not accelerate spasm cessation. CPP-115 did not alter neurodevelopmental outcomes or visuospatial learning. SIGNIFICANCE: We provide proof-of-concept evidence that CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of IS at considerably lower and better tolerated doses than vigabatrin did in our previous studies. Further optimization of the treatment protocol is needed. CPP-115 may be a promising new candidate treatment for IS with better tolerability than vigabatrin.


Assuntos
Anticonvulsivantes/uso terapêutico , Prolina/análogos & derivados , Espasmos Infantis/tratamento farmacológico , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Lactente , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Monitorização Fisiológica , Prolina/uso terapêutico , Ratos
12.
Neural Plast ; 2011: 527605, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21826277

RESUMO

The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABA(A) signaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABA(A) receptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABA(A) signaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain.


Assuntos
Epilepsia/metabolismo , Receptores de GABA-A/metabolismo , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismo , Envelhecimento/metabolismo , Pré-Escolar , Epilepsia/complicações , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Canais de Potássio/metabolismo , Fatores de Risco , Convulsões/etiologia , Convulsões/metabolismo , Fatores Sexuais
13.
J Gen Physiol ; 137(6): 521-31, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21624946

RESUMO

Anthrax toxin is composed of three proteins: a translocase heptameric channel, (PA(63))(7), formed from protective antigen (PA), which allows the other two proteins, lethal factor (LF) and edema factor (EF), to translocate across a host cell's endosomal membrane, disrupting cellular homeostasis. (PA(63))(7) incorporated into planar phospholipid bilayer membranes forms a channel capable of transporting LF and EF. Protein translocation through the channel can be driven by voltage on a timescale of seconds. A characteristic of the translocation of LF(N), the N-terminal 263 residues of LF, is its S-shaped kinetics. Because all of the translocation experiments reported in the literature have been performed with more than one LF(N) molecule bound to most of the channels, it is not clear whether the S-shaped kinetics are an intrinsic characteristic of translocation kinetics or are merely a consequence of the translocation in tandem of two or three LF(N)s. In this paper, we show both in macroscopic and single-channel experiments that even with only one LF(N) bound to the channel, the translocation kinetics are S shaped. As expected, the translocation rate is slower with more than one LF(N) bound. We also present a simple electrodiffusion model of translocation in which LF(N) is represented as a charged rod that moves subject to both Brownian motion and an applied electric field. The cumulative distribution of first-passage times of the rod past the end of the channel displays S-shaped kinetics with a voltage dependence in agreement with experimental data.


Assuntos
Antígenos de Bactérias/metabolismo , Bacillus anthracis/metabolismo , Toxinas Bacterianas/metabolismo , Transporte Proteico/fisiologia , Antígenos de Bactérias/química , Toxinas Bacterianas/química , Membrana Celular , Modelos Moleculares , Mutação , Conformação Proteica
14.
Neurobiol Dis ; 43(2): 322-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21504792

RESUMO

Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle was given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Sirolimo/farmacologia , Espasmos Infantis/tratamento farmacológico , Animais , Animais Recém-Nascidos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Modelos Animais de Doenças , Esquema de Medicação , Humanos , Recém-Nascido , Masculino , Ratos , Ratos Sprague-Dawley , Sirolimo/uso terapêutico , Espasmos Infantis/complicações , Espasmos Infantis/prevenção & controle , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia
15.
Epilepsia ; 52(3): 497-506, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21204826

RESUMO

PURPOSE: To investigate whether striatal enriched protein tyrosine phosphatase (STEP) influences ictogenesis. METHODS: STEP knockout mice were compared to wild-type (WT) mice in pilocarpine-induced seizures. Hippocampal slices were also prepared from these two mouse populations, allowing the examination of ictal-like stimulation in these slices using calcium imaging and electrophysiologic recordings. KEY FINDINGS: To examine seizure thresholds, increasing doses of pilocarpine were administered to adult mice and seizures were scored behaviorally. Significantly fewer STEP knockout mice developed seizures that progressed to the stage of status epilepticus compared to WT mice. To examine potential differences in neural circuits that might account for this finding, seizure-like activity was induced in hippocampal slices. Electrical stimulation of the hippocampal-entorhinal cortex pathway in STEP knockout mice resulted in less activation of the dentate gyrus granule cell layer (GCL), but greater activation of the hilus in STEP knockouts, compared with heterozygous slices. SIGNIFICANCE: STEP deficiency is associated with higher seizure thresholds. The locus of these effects appears to include the dentate gyrus granule cell layer and hilus.


Assuntos
Eletroencefalografia , Hipocampo/fisiopatologia , Proteínas Tirosina Fosfatases não Receptoras/genética , Convulsões/genética , Processamento de Sinais Assistido por Computador , Animais , Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiopatologia , Eletroencefalografia/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Agonistas Muscarínicos , Técnicas de Patch-Clamp , Pilocarpina , Proteínas Tirosina Fosfatases não Receptoras/efeitos dos fármacos , Convulsões/induzido quimicamente , Técnicas de Cultura de Tecidos
16.
Proc Natl Acad Sci U S A ; 107(21): 9897-902, 2010 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-20445098

RESUMO

Intracellular pH (pH(i)) can change during physiological and pathological conditions causing significant changes of electrical and metabolic cell-cell communication through gap junction (GJ) channels. In HeLa cells expressing wild-type connexin45 (Cx45) as well as Cx45 and Cx43 tagged with EGFP, we examined how pH(i) affects junctional conductance (g(j)) and g(j) dependence on transjunctional voltage (V(j)). To characterize V(j) gating, we fit the g(j)-V(j) relation using a stochastic four-state model containing one V(j)-sensitive gate in each apposed hemichannel (aHC); aHC open probability was a Boltzmann function of the fraction of V(j) across it. Using the model, we estimated gating parameters characterizing sensitivity to V(j) and number of functional channels. In homotypic Cx45 and heterotypic Cx45/Cx43-EGFP GJs, pH(i) changes from 7.2 to approximately 8.0 shifted g(j)-V(j) dependence of Cx45 aHCs along the V(j) axis resulting in increased probability of GJ channels being in the fully open state without change in the slope of g(j) dependence on V(j). In contrast, acidification shifted g(j)-V(j) dependence in the opposite direction, reducing open probability; acidification also reduced the number of functional channels. Correlation between the number of channels in Cx45-EGFP GJs and maximal g(j) achieved under alkaline conditions showed that only approximately 4% of channels were functional. The acid dissociation constant (pK(a)) of g(j)-pH(i) dependence of Cx45/Cx45 GJs was approximately 7. The pK(a) of heterotypic Cx45/Cx43-EGFP GJs was lower, approximately 6.7, between the pK(a)s of Cx45 and Cx43-EGFP (approximately 6.5) homotypic GJs. In summary, pH(i) significantly modulates junctional conductance of Cx45 by affecting both V(j) gating and number of functional channels.


Assuntos
Conexina 43/metabolismo , Conexinas/metabolismo , Junções Comunicantes/metabolismo , Ativação do Canal Iônico , Comunicação Celular , Conexina 43/genética , Conexinas/genética , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Técnicas de Patch-Clamp
17.
Crisis ; 28(3): 140-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17992827

RESUMO

This paper evaluates the contribution to suicide prevention made by an innovative project, Maytree, a respite center for the suicidal. Maytree offers a distinctive brief period of sanctuary for four nights for suicidal people; within this limited time it aims to provide opportunities through talking, reflecting, and relaxing for reducing the intense feelings that lead to suicidal behavior. The focus of this paper is on evaluating the first 3 years of Maytree's operation, exploring how Maytree works, and its effects on the people who stay there as "guests". This shows that Maytree reaches people who are at significant risk of suicide. Guests report both short term relief and longer term benefits. These changes are understood, through applying crisis intervention theory, as being generated by the opportunities for change in the Maytree approach. Thus, there is the potential for a benign cycle to be established. Maytree's model is different from that of mainstream, statutory services; we conclude that Maytree complements these services and also challenges the values and frameworks of statutory provision in the field of suicide prevention.


Assuntos
Intervenção em Crise , Desenvolvimento de Programas , Cuidados Intermitentes/métodos , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Nature ; 448(7152): 439-44, 2007 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-17611497

RESUMO

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.


Assuntos
Proteínas Sanguíneas/química , Transformação Celular Neoplásica/genética , Mutação/genética , Neoplasias/genética , Fosfoproteínas/química , Proteínas Proto-Oncogênicas c-akt/química , Proteínas Proto-Oncogênicas c-akt/genética , Homologia de Sequência de Aminoácidos , Animais , Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Análise Mutacional de DNA , Ativação Enzimática/genética , Feminino , Humanos , Leucemia/genética , Camundongos , Modelos Moleculares , Neoplasias/patologia , Neoplasias Ovarianas/genética , Estrutura Terciária de Proteína/genética , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Injury ; 38(10): 1189-96, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17582414

RESUMO

BACKGROUND: Intertrochanteric hip fractures have become more common as the elderly population continues to increase, and surgical stabilisation of these fractures remains a persistent challenge. The purpose of this study was to analyse the ability of a new helical blade device to stabilise intertrochanteric hip fractures, and to further determine which factors are important in implant stability. METHODS: Two hundred and fifty-five patients with an intertrochanteric hip fracture were treated with a trochanteric fixation nail (TFN), 97 of whom fit strict radiographic and follow-up criteria and were included in the study group. After adjusting for magnification and rotation, blade migration within the femoral head and telescoping of the blade along its axis were measured using a custom-designed grid system. Multivariate regression analyses were performed to determine which variables predicted blade migration and telescoping. RESULTS: Fifty-nine fractures were classified as stable, and the remaining 38 were unstable. Mean telescoping was 4.3 mm in the unstable group, compared to 2.6 mm in the stable group (p<0.05). Blade migration within the femoral head averaged 2.2 mm overall, with no difference between stable and unstable fractures. For both telescoping and blade migration, no significant change occurred after the 6-week time point in the stable or unstable group. Nail length, age, and gender did not have a significant effect on either blade migration or telescoping implant position change. Of the initial cohort of 255 patients, five cutouts and one nonunion occurred, three of which required subsequent procedures. CONCLUSIONS: Subtle migration ( approximately 2mm) of the tip of the blade within the femoral head occurred in all fractures, but this did not preclude maintenance of reduction and fracture healing, and was not predicted by fracture type, reduction quality, age, or gender. More telescoping occurred in unstable compared to stable fractures, but this averaged 4mm and did not affect stable fixation or fracture healing. All position changes occurred within the first 6 weeks postoperatively, with no subsequent detectable migration or telescoping. Clinical correlations will be needed in the future to determine the significance of small amounts of migration or differences in telescoping, but this device appears to provide effective fixation in both stable and unstable intertrochanteric hip fractures.


Assuntos
Pinos Ortopédicos , Fixação Interna de Fraturas/instrumentação , Fraturas do Quadril/diagnóstico por imagem , Idoso , Feminino , Fêmur/cirurgia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
20.
Arch Orthop Trauma Surg ; 127(3): 223-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17195932

RESUMO

INTRODUCTION: Restoration of gait is a particularly important patient-based functional outcome following lower extremity trauma. A new portable device which measures gait parameters, the IDEEA, may be particularly useful in evaluating post-traumatic gait parameters in the office setting, but the accuracy and repeatability of this device relative to standard gait laboratory footswitches are unknown. MATERIAL AND METHODS: Twelve healthy subjects were tested simultaneously using the IDEEA device and standard gait laboratory footswitches, at slow, medium, and fast speeds. Parameters evaluated were single-limb support time (SLS), double-limb support time (DLS), swing phase duration (SPD), cycle duration, and cadence. RESULTS: The repeatability between right and left measurements tended to be better for the IDEEA, and was at least as good as the foot switches. The absolute differences of the timed gait parameters between the two devices were all in the range of 0.03 s, which is within the data sampling resolution of the gait laboratory foot switches (0.04 s). Furthermore, assuming a 1-s gait cycle, these differences account for only 3% of the gait cycle, which is also well within the clinical parameters for evaluating and differentiating between treatments. CONCLUSION: This device is accurate and repeatable, and may facilitate the evaluation of gait function in post-traumatic patients in settings outside of the traditional gait laboratory.


Assuntos
Marcha/fisiologia , Monitorização Fisiológica/instrumentação , Adulto , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes
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