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1.
Br J Neurosurg ; 36(2): 192-195, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33470851

RESUMO

BACKGROUND: Hyponatraemia is a common complication of aneurysmal subarachnoid haemorrhage (SAH). We aimed to determine current neurosurgical practice for the identification, investigation and management of hyponatraemia after SAH. METHODS: An online questionnaire was completed by UK and Irish neurosurgical trainees and consultant collaborators in the Sodium after Subarachnoid Haemorrhage (SaSH) audit. RESULTS: Between August 2019 and June 2020, 43 responses were received from 31 of 32 UK and Ireland adult neurosurgical units (NSUs). All units reported routine measurement of serum sodium either daily or every other day. Most NSUs reported routine investigation of hyponatraemia after SAH with paired serum and urinary osmolalities (94%), urinary sodium (84%), daily fluid balance (84%), but few measured glucose (19%), morning cortisol (13%), or performed a short Synacthen test (3%). Management of hyponatraemia was variable, with units reporting use of oral sodium supplementation (77%), fluid restriction (58%), hypertonic saline (55%), and fludrocortisone (19%). CONCLUSIONS: Reported assessment of serum sodium after SAH was consistent between units, whereas management of hyponatraemia varied. This may reflect the lack of a specific evidence-base to inform practice.


Assuntos
Hiponatremia , Hemorragia Subaracnóidea , Adulto , Humanos , Hiponatremia/etiologia , Hiponatremia/terapia , Irlanda , Sódio , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Inquéritos e Questionários , Reino Unido
2.
Cochrane Database Syst Rev ; 6: CD013156, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114650

RESUMO

BACKGROUND: The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD. OBJECTIVES: To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods. MAIN RESULTS: We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention. AUTHORS' CONCLUSIONS: The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitudinal cohorts of participants to gain efficiencies and align trials more closely to standard clinical practice), comparing aerobic exercise and dietary advice versus standard of care (exercise and dietary advice received as part of national health promotion). The reason for the choice of aerobic exercise and dietary advice is the impact of these interventions on indirect outcomes which may translate to clinical benefit. The outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource use measures including costs of intervention and decreased healthcare use after a minimum follow-up of eight years, to find meaningful differences in the clinically important outcomes.


Assuntos
Estilo de Vida , Hepatopatia Gordurosa não Alcoólica/terapia , Teorema de Bayes , Viés , Restrição Calórica , Dieta com Restrição de Carboidratos , Dieta Mediterrânea , Exercício Físico , Seguimentos , Humanos , Metanálise em Rede , Hepatopatia Gordurosa não Alcoólica/complicações , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento Resistido , Fatores de Tempo
3.
J Behav Med ; 44(4): 527-540, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33772702

RESUMO

Maintenance of weight loss is hard to achieve, and novel interventions are needed to improve long-term outcomes. In this pilot randomized controlled trial, N = 188 participants received an online, 12-week weight loss intervention and N = 102 who lost ≥ 5% were then randomly assigned to a 1-day, 5-h workshop based on Acceptance and Commitment Therapy (ACT), Self-Regulation (SR), or no workshop (Control) with 3 months of limited email follow-up. Assessments were conducted at baseline, 3, 6, 12, 18, and 24 months. The primary outcome was percent weight change; secondary outcomes were weight-related experiential avoidance and health values-consistent behavior. ACT had greater overall weight loss (-7.18%, SE = 1.33) when compared to Control (-1.15%, SE = 1.50; p = .03). Post hoc analyses showed that ACT had significantly greater weight losses than Control (6.11%, ß = -2.03, p = .048) among those with lower initial weight loss (5-7%), and significantly greater weight loss than SR (6.19%, ß = -1.77, p = .05) among those with the highest initial weight losses (10% +). There is potential for continuing to develop ACT in a limited interventionist-contact format with modifications. This pilot study represents an innovative model for behavioral weight loss by reversing the typical treatment intensity model with the aim of providing interventionist support during a critical period after initial weight loss. REGISTRATION: Clinicaltrials.org #NCT02156752 https://www.clinicaltrials.gov/ct2/show/NCT02156752 .


Assuntos
Terapia de Aceitação e Compromisso , Autocontrole , Humanos , Obesidade , Projetos Piloto , Redução de Peso
4.
J Strength Cond Res ; 35(1): 47-55, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29847531

RESUMO

ABSTRACT: Angelino, D, McCabe, TJG, and Earp, JE. Comparing acceleration and change of direction ability between backpedal and cross-over run techniques for use in American football. J Strength Cond Res 35(1): 47-55, 2021-In American football, defensive backs guard receivers using either cross-over (CO) run or backpedal (BP) techniques, but the efficacy of these techniques is unknown. The purpose of this study was to compare linear acceleration (LA) and change of direction (CoD) ability when using CO and BP. Collegiate football defensive backs participated in LA (n = 13) and CoD (n = 7) testing. During LA, subjects performed CO, BP, and forward sprints with split times taken between 0-3 and 3-5 yd and ground reaction forces recorded 0 and 3 yd from the start. During CoD testing, subjects performed the CO or BP for 3 yd and then were given a cue to sprint to a gate 5 yd away in 1 of 4 directions (downfield, midfield, sideline, or upfield). In LA, CO was faster than BP between 0-3 yd (Δ -0.20 ± 0.02 seconds, p = 0.000) and 3-5 yd (Δ -0.12 ± 0.02 seconds, p = 0.000). At the start of the movement, CO demonstrated greater propulsive forces (p = 0.017). However, 3 yd from the start, CO demonstrated greater propulsive forces and reduced braking forces (p = 0.000 & 0.003). In CoD, CO was faster than BP when running in the downfield (Δ 0.21 ± 0.05 seconds, p = 0.044) and lateral directions (Δ 0.21 ± 0.08 seconds, p = 0.035), but similar in the upfield direction (Δ 0.01 ± 0.08, p = 0.986). Our results indicate that CO is superior to BP in LA, CoD ability, and movement efficiency and support the use of CO for defensive backs.


Assuntos
Desempenho Atlético , Futebol Americano , Corrida , Aceleração , Humanos , Tempo , Estados Unidos
5.
BMC Med Educ ; 18(1): 152, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29945579

RESUMO

BACKGROUND: Mobile learning (mLearning) devices (such as tablets and smartphones) are increasingly part of the clinical environment but there is a limited and somewhat conflicting literature regarding the impact of such devices in the clinical learning environment. This study aims to: assess the impact of mLearning devices in the clinical learning environment on medical students' studying habits, attitudes towards mobile device supported learning; and the perceived reaction of clinicians and patients to the use of these devices as part of learning in the clinical setting. METHODS: Over three consecutive academic years, 18 cohorts of medical students (total n = 275) on a six-week rotation at a large teaching hospital in London were supplied with mLearning devices (iPad mini) to support their placement-based learning. Feedback on their experiences and perceptions was collected via pre- and post-use questionnaires. RESULTS: The results suggest mLearning devices have a positive effect on the students' perceived efficiency of working, while experience of usage not only confirmed pre-existing positive opinions about devices but also disputed some expected limitations associated with mLearning devices in the clinical workplace. Students were more likely to use devices in 'down-time' than as part of their clinical learning. As anticipated, both by users and from the literature, universal internet access was a major limitation to device use. The results were inconclusive about the student preference for device provision versus supporting a pre-owned device. CONCLUSION: M-learning devices can have a positive impact on the learning experiences medical students during their clinical attachments. The results supported the feasibility of providing mLearning devices to support learning in the clinical environment. However, universal internet is a fundamental limitation to optimal device utilisation.


Assuntos
Atitude do Pessoal de Saúde , Telefone Celular , Computadores de Mão , Educação Médica/métodos , Aprendizagem , Estudantes de Medicina/psicologia , Adulto , Feminino , Hospitais de Ensino , Humanos , Londres , Masculino , Percepção , Inquéritos e Questionários , Adulto Jovem
6.
Int J Obes (Lond) ; 41(3): 467-470, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28025574

RESUMO

Higher preoperative physical activity (PA) strongly predicts higher post-operative PA in bariatric surgery (BS) patients, providing rationale for preoperative PA interventions (PAIs). However, whether PAI-related increases can be maintained post-operatively has not been examined. This study compared PA changes across pre- (baseline, post-intervention) and post-operative (6-month follow up) periods in participants randomized to 6 weeks of preoperative PAI or standard care control (SC). Of 75 participants initially randomized, 36 (PAI n=22; SC n=14) underwent BS. Changes in daily bout-related (⩾10-min bouts) moderate-to-vigorous PA (MVPA) and steps were assessed via the SenseWear Armband monitor. PAI received weekly counseling to increase walking exercise. Retention (86%) at post-operative follow up was similar between groups. Intent-to-treat analyses showed that PAI vs SC had greater increases across time (baseline, post-intervention, follow up) in bout-related MVPA minutes/day (4.3±5.1, 26.3±21.3, 28.7±26.3 vs 10.4±22.9, 11.4±16.0, 18.5±28.2; P=0.013) and steps/day (5163±2901, 7950±3286, 7870±3936 vs 5163±2901, 5601±3368, 5087±2603; P<0.001). PAI differed from SC on bout-related MVPA at post-intervention (P=0.016; d=0.91), but not follow up (P=0.15; d=0.41), and steps at post-intervention (P=0.031; d=0.78) and follow up (P=0.024; d=0.84). PAI participants maintained preoperative PA increases post-operatively. Findings support preoperative PAIs and research to test whether PA changes can be sustained and influence surgical outcomes beyond the initial post-operative period.


Assuntos
Cirurgia Bariátrica , Exercício Físico/fisiologia , Comportamentos Relacionados com a Saúde , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Exercício Físico/psicologia , Feminino , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Obesidade Mórbida/prevenção & controle , Período Pré-Operatório , Caminhada
7.
Proc Natl Acad Sci U S A ; 111(18): E1924-32, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24753613

RESUMO

Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.


Assuntos
Células-Tronco Adultas/fisiologia , Androgênios/fisiologia , Desenvolvimento Fetal/fisiologia , Células Intersticiais do Testículo/fisiologia , Células-Tronco Adultas/efeitos dos fármacos , Animais , Callithrix , Linhagem da Célula/fisiologia , Dibutilftalato/toxicidade , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Células-Tronco Fetais/efeitos dos fármacos , Células-Tronco Fetais/fisiologia , Humanos , Técnicas In Vitro , Células Intersticiais do Testículo/efeitos dos fármacos , Hormônio Luteinizante/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais , Gravidez , Ratos , Ratos Transgênicos , Ratos Wistar , Receptores Androgênicos/deficiência , Receptores Androgênicos/genética , Receptores Androgênicos/fisiologia , Regeneração , Testículo/embriologia , Testículo/fisiologia , Testosterona/deficiência , Testosterona/fisiologia
8.
Angew Chem Int Ed Engl ; 56(31): 9058-9061, 2017 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-28609604

RESUMO

Two classes of novel sulfonated phenylated polyphenylene ionomers are investigated as polyaromatic-based proton exchange membranes. Both types of ionomer possess high ion exchange capacities yet are insoluble in water at elevated temperatures. They exhibit high proton conductivity under both fully hydrated conditions and reduced relative humidity, and are markedly resilient to free radical attack. Fuel cells constructed with membrane-electrode assemblies containing each ionomer membrane yield high in situ proton conductivity and peak power densities that are greater than obtained using Nafion reference membranes. In situ chemical stability accelerated stress tests reveal that this class of the polyaromatic membranes allow significantly lower gas crossover and lower rates of degradation than Nafion benchmark systems. These results point to a promising future for molecularly designed sulfonated phenylated polyphenylenes as proton-conducting media in electrochemical technologies.

9.
Anal Biochem ; 504: 1-3, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27040182

RESUMO

We simulated, using Comsol Multiphysics, the excretion of antibodies by single hybridoma cells and their subsequent binding on a surface plasmon resonance imaging (SPRi) sensor. The purpose was to confirm that SPRi is suitable to accurately quantify antibody (anti-EpCAM) excretion. The model showed that antibody loss by diffusion away from the sensor was less than 1%. Unexpectedly, more than 99% of the excreted antibodies were captured on the sensor. These data prove the remarkable phenomenon that the SPRi output of cellular antibody excretion and its subsequent binding, performed under the conditions described here, is directly usable for quantification of single cell antibody production rates.


Assuntos
Anticorpos/metabolismo , Formação de Anticorpos , Hibridomas/imunologia , Hibridomas/metabolismo , Ressonância de Plasmônio de Superfície , Anticorpos/imunologia , Difusão , Molécula de Adesão da Célula Epitelial/imunologia , Humanos , Hibridomas/patologia
10.
J Am Chem Soc ; 137(38): 12223-6, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26375041

RESUMO

We report the synthesis and molecular characterization of structurally defined, sulfo-phenylated, oligo- and polyphenylenes that incorporate a novel tetra-sulfonic acid bistetracyclone monomer. The utility of this monomer in the [4 + 2] Diels-Alder cycloaddition to produce well-defined, sulfonated oligophenylenes and pre-functionalized polyphenylene homopolymers is demonstrated. Characterization of the oligophenylenes indicates formation of the meta-meta and para-para adducts in a ∼ 1:1 ratio. These functionalized monomers and their subsequent coupling provide a route to prepare novel, sterically encumbered, sulfonated polyphenylenes possessing unprecedented structural control.

11.
Anal Biochem ; 485: 112-8, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26095397

RESUMO

Surface plasmon resonance imaging (SPRi) is most frequently used for the label-free measurement of biomolecular interactions. Here we explore the potential of SPRi to measure antibody production of individual hybridoma cells. As a model system, cells from a hybridoma, producing monoclonal antibodies recognizing epithelial cell adhesion molecule (EpCAM), were used. Recombinant human EpCAM protein was immobilized on an SPR sensor and hybridoma cells were introduced into an IBIS MX96 SPR imager and the SPRi response was followed for 10h. SPRi responses were detected on the spots of the sensor only where ligands of the produced antibody were present. By measuring the SPRi signals on individual cells the antibody production of the individual cells was measured and production rates were calculated. For 53 single EpCAM hybridoma cells the production ranged from 0.16 to 11.95 pg (mean 2.96p g per cell, SD 2.51) over a period of 10 h. Antibody excretion per cell per hour ranged from 0.02 to 1.19 pg (mean 0.30, SD 0.25). Here we demonstrate for the first time that antibody production of individual cells can be measured and quantified by SPRi, opening a new avenue for measuring excretion products of individual cells.


Assuntos
Anticorpos/metabolismo , Hibridomas/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Animais , Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Moléculas de Adesão Celular/imunologia , Molécula de Adesão da Célula Epitelial , Humanos , Hibridomas/citologia , Hibridomas/imunologia , Camundongos
12.
BMJ Open ; 13(3): e068801, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36972969

RESUMO

OBJECTIVES: To assess the frequency of discharge against medical advice (DAMA) in a large UK teaching hospital, explore factors which increase the risk of DAMA and identify how DAMA impacts patient risk of mortality and readmission. DESIGN: Retrospective cohort study. SETTING: Large acute teaching hospital in the UK. PATIENTS: 36 683 patients discharged from the acute medical unit of a large UK teaching hospital between 1 January 2012 and 31 December 2016. MEASUREMENTS: Patients were censored on 1 January 2021. Mortality and 30-day unplanned readmission rates were assessed. Deprivation, age and sex were taken as covariates. RESULTS: 3% of patients discharged against medical advice. These patients were younger (median age (years) (IQR)): planned discharge (PD) 59 (40-77); DAMA 39 (28-51), predominantly of male sex (PD 48%; DAMA 66%) and were of greater social deprivation (in three most deprived quintiles PD 69%; DAMA 84%). DAMA was associated with increased risk of death in patients under the age of 33.3 years (adjusted HR 2.6 (1.2-5.8)) and increased incidence of 30-day readmission (standardised incidence ratio 1.9 (1.5-2.2)). LIMITATIONS: Readmission to acute hospitals outside of the local health board may have been missed. We were unable to include information regarding comorbidity or severity of presentation. CONCLUSIONS: These data highlight the vulnerability of younger patients who DAMA, even in a free-at-the-point-of-delivery healthcare setting.


Assuntos
Alta do Paciente , Readmissão do Paciente , Humanos , Masculino , Adulto , Estudos Retrospectivos , Hospitais de Ensino , Reino Unido/epidemiologia
13.
Nat Commun ; 14(1): 1409, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918610

RESUMO

Natural killer cells are considered to be important for control of human cytomegalovirus- a major pathogen in immune suppressed transplant patients. Viral infection promotes the development of an adaptive phenotype in circulating natural killer cells that changes their anti-viral function. In contrast, less is understood how natural killer cells that reside in tissue respond to viral infection. Here we show natural killer cells resident in the liver have an altered phenotype in cytomegalovirus infected individuals and display increased anti-viral activity against multiple viruses in vitro and identify and characterise a subset of natural killer cells responsible for control. Crucially, livers containing natural killer cells with better capacity to control cytomegalovirus replication in vitro are less likely to experience viraemia post-transplant. Taken together, these data suggest that virally induced expansion of tissue resident natural killer cells in the donor organ can reduce the chance of viraemia post-transplant.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Humanos , Viremia , Células Matadoras Naturais , Fígado
14.
Stroke Vasc Neurol ; 8(3): 207-216, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36150732

RESUMO

BACKGROUND: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. METHODS: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. RESULTS: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I-III, modified Fisher 2-4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. CONCLUSIONS: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care.


Assuntos
Hemorragia Subaracnóidea , Humanos , Irlanda/epidemiologia , Estudos Prospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/terapia , Hospitalização , Sódio , Estudos Multicêntricos como Assunto
15.
J Neuroendocrinol ; 34(7): e13165, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35833423

RESUMO

Glucocorticoids (GC) are prescribed for periods > 3 months to 1%-3% of the UK population; 10%-50% of these patients develop hypothalamus-pituitary-adrenal (HPA) axis suppression, which may last over 6 months and is associated with morbidity and mortality. Recovery of the pituitary and hypothalamus is necessary for recovery of adrenal function. We developed a mouse model of dexamethasone (DEX)-induced HPA axis dysfunction aiming to further explore recovery in the pituitary. Adult male wild-type C57BL6/J or Pomc-eGFP transgenic mice were randomly assigned to receive DEX (approximately 0.4 mg kg-1 bodyweight day-1 ) or vehicle via drinking water for 4 weeks following which treatment was withdrawn and tissues were harvested after another 0, 1, and 4 weeks. Corticotrophs were isolated from Pomc-eGFP pituitaries using fluorescence-activated cell sorting, and RNA extracted for RNA-sequencing. DEX treatment suppressed corticosterone production, which remained partially suppressed at least 1 week following DEX withdrawal. In the adrenal, Hsd3b2, Cyp11a1, and Mc2r mRNA levels were significantly reduced at time 0, with Mc2r and Cyp11a1 remaining reduced 1 week following DEX withdrawal. The corticotroph transcriptome was modified by DEX treatment, with some differences between groups persisting 4 weeks following withdrawal. No genes supressed by DEX exhibited ongoing attenuation 1 and 4 weeks following withdrawal, whereas only two genes were upregulated and remained so following withdrawal. A pattern of rebound at 1 and 4 weeks was observed in 14 genes that increased following suppression, and in six genes that were reduced by DEX and then increased. Chronic GC treatment may induce persistent changes in the pituitary that may influence future response to GC treatment or stress.


Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico/metabolismo , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol , Corticosterona , Corticotrofos/metabolismo , Dexametasona/farmacologia , Glucocorticoides , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/metabolismo , Masculino , Camundongos , Sistema Hipófise-Suprarrenal/metabolismo , Pró-Opiomelanocortina/genética , RNA
16.
J Wound Care ; 20(3): 124,126-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21537295

RESUMO

OBJECTIVE: To test the antimicrobial effectiveness of a silver alginate dressing on opportunistic pathogens, namely meticillin-sensitive Staphylococcus aureus (MSSA) and meticillin-resistant Staphylococcus aureus (MRSA), Klebsiella spp., Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sakazakii, Enterobacter cloacae, Serratia marcescens, Chryseobacterium indologenes, Proteus vulgaris and Acinetobacter baumannii. METHOD: In total, 40 microorganisms were isolated from patients attending three burn centres in the US and evaluated for their susceptibility to a silver alginate wound dressing, employing a corrected zone of inhibition assay, conducted on Mueller Hinton agar (MHA). RESULTS: The sizes of the corrected zones of inhibition varied between and within genera. For example, all Acinetobacter baumannii strains were found to be sensitive to ionic silver at pH 7, with a mean of 2.8mm, compared with 3.5mm at pH 5.5. The silver alginate dressing also demonstrated activity on all strains of Enterobacter and Escherichia coli, with susceptibility to the silver alginate dressing enhanced at pH 5.5. For Enterococcus spp. the average corrected zone of inhibition at pH 7 was 3.6mm, versus 4.9mm at pH 5.5. All strains of Pseudomonas aeruginosa were found to be sensitive to the silver alginate dressing. The average corrected zone of inhibition was 6.9mm at pH 7, compared with 8mm at pH 5.5. For MRSA and Staphylococcus aureus, it ranged from 4.5mm to 7.5mm at pH 7. When the pH was decreased to 5.5, the corrected zone of inhibition increased. CONCLUSION: This study demonstrates the activity of a silver alginate dressing on a wide range of burn isolates, including antibiotic-resistant bacteria, isolated from three different burn centres in the US. It also highlights the possible importance of pH and its potential effects on antimicrobial performance and microbial susceptibility. However, more extensive testing is required to substantiate this. CONFLICT OF INTEREST: SLP is employed by Advanced Medical Solutions Ltd.


Assuntos
Alginatos/uso terapêutico , Queimaduras/microbiologia , Curativos Oclusivos , Cicatrização , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana/métodos , Prata/farmacologia
17.
J Wound Care ; 20(12): 580-2, 584-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22240884

RESUMO

OBJECTIVE: To evaluate and compare the efficacy of a silver alginate (SA) dressing and a silver carboxymethyl cellulose (SCMC) dressing on burn isolates grown within the quasi/non-biofilm state and the biofilm phenotypic states. METHOD: Antimicrobial activity was tested using 46 burn wound isolates with a corrected zone of inhibition (CZOI) assay on agar (quasi/non-biofilm) and poloxamer (biofilm). RESULTS: All Gram-negative and positive isolates evaluated were found to be sensitive to both silver containing wound dressings, although superior antimicrobial activity was observed for a select number of specific bacteria when grown in the quasi/non-biofilm phenotypic state, for the SCMC dressing. However, the majority of isolates demonstrated reduced sensitivity to silver when grown as a biofilm, compared with growth in the quasi/non-biofilm phenotypic state. Both dressings demonstrated equivalent antimicrobial activity on Gram-negative isolates grown in the biofilm phenotypic state. For the Gram-positive isolates growing in the biofilm phenotypic state, there appeared to be greater sensitivity to the SA dressing compared with the SCMC dressing, although this result was not statistically significant. CONCLUSION: This study demonstrated the antimicrobial effectiveness of an SA and SCMC dressing in inhibiting the growth of burn isolates residing in both the quasi/non-biofilm and biofilm phenotypic states. It also suggests the SA dressing could be more effective on Gram-positive isolates grown in the biofilm phenotypic state, compared with SCMC dressing.


Assuntos
Bandagens , Queimaduras/microbiologia , Compostos de Prata/administração & dosagem , Infecção dos Ferimentos/prevenção & controle , Alginatos , Queimaduras/terapia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Metilcelulose
18.
Obes Sci Pract ; 5(1): 21-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30847224

RESUMO

OBJECTIVE: Despite the myriad negative effects of weight self-stigma, its role in weight loss intervention has not been thoroughly examined. The aim of this study was to examine the association between weight self-stigma and weight loss. METHODS: This longitudinal study examined the association between weight loss and changes in self-stigma, assessed by the Weight Self-Stigma Questionnaire, which distinguished between self-devaluation and fear of enacted stigma. Participants were adults with overweight or obesity enrolled in a 24-month weight loss intervention trial (groups were collapsed for this post hoc analysis) who were assessed at baseline, 6, 12, 18 and 24 months. RESULTS: Baseline levels of self-stigma were not associated with weight loss outcomes. However, mixed models analysis showed that reductions in one aspect of weight self-stigma, self-devaluation, was associated with greater weight loss (p = 0.01). Cross products mediation analysis showed that increases in use of weight control strategies mediated the association between reductions in self-devaluation and greater weight loss (F = 14.86, p < 0.001; CI 0.09-0.37). CONCLUSIONS: Results suggest that there may be potential for incorporating intervention methods targeting the reduction of self-stigma in order to improve weight loss outcomes.

19.
Biosensors (Basel) ; 9(2)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137820

RESUMO

Rapid multiplex cell surface marker analysis can expedite investigations in which large number of antigens need to be analyzed. Simultaneous analysis of multiple surface antigens at the same level of sensitivity is however limited in the current golden standard analysis method, flow cytometry. In this paper we introduce a surface plasmon resonance imaging (SPRi)-based technique for 44-plex parameter analysis using a single sample, in less than 20 min. We analyzed the expression on cells from five different cancer cell lines by SPRi on a 44-plex antibody array including 4 negative controls and compared the output with flow cytometry. The combined correlation of the markers that showed expression by flow cytometry was 0.76. The results demonstrate as a proof of principle that SPRi can be applied for rapid semi-quantitative multiplex cell surface marker analysis.


Assuntos
Antígenos de Neoplasias/análise , Citometria de Fluxo/métodos , Ressonância de Plasmônio de Superfície/métodos , Humanos , Células MCF-7
20.
Nat Commun ; 10(1): 2306, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127108

RESUMO

Solid polymer electrolyte electrochemical energy conversion devices that operate under highly alkaline conditions afford faster reaction kinetics and the deployment of inexpensive electrocatalysts compared with their acidic counterparts. The hydroxide anion exchange polymer is a key component of any solid polymer electrolyte device that operates under alkaline conditions. However, durable hydroxide-conducting polymer electrolytes in highly caustic media have proved elusive, because polymers bearing cations are inherently unstable under highly caustic conditions. Here we report a systematic investigation of novel arylimidazolium and bis-arylimidazolium compounds that lead to the rationale design of robust, sterically protected poly(arylimidazolium) hydroxide anion exchange polymers that possess a combination of high ion-exchange capacity and exceptional stability.

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