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1.
Mem Cognit ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378883

RESUMEN

Research has demonstrated that individuals can direct their attention to valuable information in both working memory and long-term memory tasks with observable effects on performance. However, it is currently unclear whether prioritising an item for a working memory task automatically translates into a boost at long-term memory. This was examined in two experiments using relatively short (250 ms per item; Experiment 1) and longer (500 ms per item; Experiment 2) encoding times. Participants first completed a visual working memory task, in which they were presented with series of photographs of everyday objects. Following a brief delay (1,000 ms), they completed a four-alternative forced-choice test. Prior to encoding, participants were informed of the point values associated with each item. In some trials, the first item in the sequence was worth more points than the rest. In other trials, all items were equally valuable. After a filled delay, participants completed a surprise long-term memory task. At working memory, a value effect was reliably observed on recognition accuracy, along with some evidence of faster response times for high-value items. However, there was little consistent evidence of this effect automatically persisting into long-term memory. Thus, the benefits of attentional prioritization in working memory do not always translate into longer-term performance. More broadly, this provides further evidence that manipulations that enhance working memory performance do not necessarily enhance long-term memory.

2.
J Microsc ; 267(3): 384-396, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28504417

RESUMEN

A robust and versatile sample preparation technique for the fabrication of cylindrical pillars for imaging by X-ray nano-computed tomography (nano-CT) is presented. The procedure employs simple, cost-effective laser micro-machining coupled with focused-ion beam (FIB) milling, when required, to yield mechanically robust samples at the micrometre length-scale to match the field-of-view (FOV) for nano-CT imaging. A variety of energy and geological materials are exhibited as case studies, demonstrating the procedure can be applied to a variety of materials to provide geometrically optimised samples whose size and shape are tailored to the attenuation coefficients of the constituent phases. The procedure can be implemented for the bespoke preparation of pillars for both lab- and synchrotron-based X-ray nano-CT investigations of a wide range of samples.

3.
Eur J Clin Microbiol Infect Dis ; 36(3): 537-544, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27885442

RESUMEN

We characterize the epidemiology of pediatric bloodstream infections (BSIs) in Switzerland. We analyzed pathogen distribution and resistance patterns in monomicrobial and polymicrobial BSIs in children from 2008 to 2014 using data from the Swiss antibiotic resistance centre (ANRESIS). A confirmatory statistical analysis was performed comparing pathogens and resistance across 20 acute care hospitals. We identified 3,067 bacteremia episodes, of which 1,823 (59 %) were considered true BSI episodes. Overall, S. aureus (16.5 %, 300) was the most frequent pathogen, followed by E. coli (15.1 %, 276), coagulase-negative staphylococci (CoNS, 12.9 %, 235), S. pneumoniae (11.1 %, 202) and non-E. coli Enterobacteriaceae (8.7 %, 159). S. aureus and E. coli showed similar frequencies in all of the variables analyzed (e.g., hospital acquisition, hospital type, medical specialty). The proportion of these microorganisms did not change over time, resistance rates remained low (4.3 % methicillin resistance in S. aureus; 7.3 % third-/fourth-generation cephalosporin resistance in E. coli), and no significant resistance trends were observed. We observed a 50 % increase of CoNS BSIs from 2008 (9.8 %, 27) to 2014 (15.2 %, 46, p value for trend = 0.03). S. pneumoniae decreased from 17.5 % (48) to 6.6 % (20) during that timeframe (p for trend = 0.007). S. aureus and E. coli remained the most significant pathogens among pediatric BSIs in Switzerland, exhibiting low resistance rates. CoNS accounted for a greater proportion of BSIs over time. The decrease in bacteremic pneumococcal infections can likely be attributed to the introduction of the 13-valent conjugate vaccine in 2011.


Asunto(s)
Bacterias/clasificación , Bacterias/aislamiento & purificación , Sepsis/epidemiología , Sepsis/patología , Adolescente , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Niño , Preescolar , Farmacorresistencia Bacteriana , Monitoreo Epidemiológico , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Sepsis/microbiología , Suiza/epidemiología
4.
Folia Morphol (Warsz) ; 75(2): 216-223, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26431048

RESUMEN

The sinus node is an intensively researched structure in terms of anatomical, histological, electrophysiological, molecular and genetic approach. For postmortem diagnosis it is still difficult to investigate due to a still reduced accessibility. In this study we tried and succeed to apply molecular biology techniques on postmortem tissues in order to widen the range of postmortem forensic investigation and provide information related to the diagnostic of cardiac arrhythmia. We described the stages of this investigation, with dissection, preservation and analysis that included classical histology, immunohistochemistry, confocal microscope, microdissection, RIN testing, mRNA expression obtaining a precise morphofunctional location of the sinus node.


Asunto(s)
Nodo Sinoatrial , Autopsia , Inmunohistoquímica , Cambios Post Mortem
5.
J Obstet Gynaecol ; 35(2): 139-41, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25093255

RESUMEN

The Kleihauer-Betke (KB) test evaluates fetal blood in the maternal circulation, and is often used when placental abruption is suspected. At our centre, it is the protocol to perform a KB test in all suspected cases of abruption. We carried out a retrospective study of all cases of abruption that occurred at our centre over 6 years. Of the 68 confirmed cases of placental abruption, only three had positive KB tests, giving a sensitivity of only 4.4%. Thus, in the overwhelming majority of cases of confirmed abruption, the KB test was negative. Our findings indicate that the KB test has poor sensitivity for placental abruption and should not be used in the detection of abruption.


Asunto(s)
Desprendimiento Prematuro de la Placenta/sangre , Desprendimiento Prematuro de la Placenta/diagnóstico , Eritrocitos , Transfusión Fetomaterna/sangre , Adulto , Reacciones Falso Negativas , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
6.
N Engl J Med ; 364(1): 43-50, 2011 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-21208107

RESUMEN

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.


Asunto(s)
Acromegalia/genética , Adenoma/genética , Gigantismo/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Neoplasias Hipofisarias/genética , Prolactinoma/genética , Acromegalia/historia , Adenoma/historia , Gigantismo/historia , Adenoma Hipofisario Secretor de Hormona del Crecimiento/historia , Haplotipos , Heterocigoto , Historia del Siglo XVIII , Humanos , Masculino , Repeticiones de Microsatélite , Linaje , Análisis de Secuencia de ADN
7.
Pituitary ; 17(4): 320-6, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23943009

RESUMEN

In a previous 15-day, Phase II study of patients with de novo or persistent/recurrent Cushing's disease (core study), treatment with pasireotide 600 µg sc bid reduced urinary free cortisol (UFC) levels in 76% of patients and normalized UFC in 17%. The objective of this study was to evaluate the efficacy and safety of extended treatment with pasireotide. This was a planned, open-ended, single-arm, multicenter extension study (primary endpoint: 6 months). Patients aged ≥18 years with Cushing's disease who completed the core study could enter the extension if they achieved UFC normalization at core study end and/or obtained significant clinical benefit. Of the 38 patients who completed the core study, 19 entered the extension and 18 were included in the efficacy analyses (three responders, 11 reducers, four non-reducers in the core study). At data cut-off, median treatment duration in the extension was 9.7 months (range: 2 months to 4.8 years). At extension month 6, 56% of the 18 patients had lower UFC than at core baseline and 22% had normalized UFC. Of the four patients who remained on study drug at month 24, one had normalized UFC. Reductions in serum cortisol, plasma adrenocorticotropic hormone, body weight and diastolic blood pressure were observed. The most common adverse events were mild-to-moderate gastrointestinal disorders and hyperglycemia. Pasireotide offers a tumor-directed medical therapy that may be effective for the extended treatment of some patients with Cushing's disease.


Asunto(s)
Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/tratamiento farmacológico , Somatostatina/análogos & derivados , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Somatostatina/uso terapéutico , Adulto Joven
8.
Br J Sociol ; 65(4): 619-38, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25516342

RESUMEN

In this paper, I take Capital in the Twenty-First Century by Thomas Piketty as the starting point for a set of twelve policy proposals that could bring about a genuine shift in the distribution of income towards less inequality. In designing the set of proposals, I draw on the experience of reducing inequality in postwar Europe and on an analysis as to how the economic circumstances are now different in the twenty-first century, highlighting the role of technical change and the rise in capital emphasized by Piketty. The proposed measures span many fields of policy, and are not confined to fiscal redistribution, encompassing science policy, competition policy, public employment, a guaranteed return on small savings, a capital endowment, as well as more progressive taxation of income and wealth transfers, and a participation income. Inequality is embedded in our social structure, and the search for a significant reduction requires us to examine all aspects of our society. I focus on inequality within countries, and what can be achieved by national governments, with the UK specifically in mind. The primary audience is those concerned with policy-making in national governments, but implementation should not be seen purely in these terms. There are different levels of government, and certain proposals, particularly those concerned with taxation, may only be feasible if pursued by a group of countries in collaboration. The last of the twelve proposals - for a basic income for children - is specifically directed at the European Union. Finally, actions by individuals as consumers, as workers, or as employers, can all contribute to reducing inequality.


Asunto(s)
Política Pública , Sociología/economía , Humanos , Impuesto a la Renta/economía , Literatura , Modelos Económicos , Política , Pobreza , Factores Socioeconómicos , Reino Unido
9.
Clin Endocrinol (Oxf) ; 78(6): 898-906, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23072324

RESUMEN

OBJECTIVES: Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts of patients with non-syndromic PPGL and head and neck paraganglioma (HNPGL). DESIGN: Prospective, observational evaluation of NHS practice. PATIENTS: Individuals with PPGL/HNPGL referred to a supraregional genetics testing service over a 10-year period. MEASUREMENTS: Clinical (age, tumour site, malignancy, etc.), mutation frequencies and characteristics. RESULTS: A total of 501 probands with PPGL (n = 413) or HNPGL (n = 88) were studied. Thirty-one percent of patients with PPGL presented had a pathogenic mutation in SDHB, SDHD or VHL. Mutation detection rates were highest in those with a positive family history (62%), malignancy (53%), multiple tumours (33%) or PGL (44%). Twenty-eight percent of individuals with a single sporadic phaeochromocytoma had a mutation. Overall, 63% of patients with HNPGL had a mutation (92% of those with a family history, 89% of those with multicentric tumours and 34% of those with a single sporadic HNPGL). Penetrance was calculated in 121 SDHB mutation-positive probands and 187 of their mutation-positive relatives. Most relatives were asymptomatic and lifetime penetrance in non-proband SDHB mutation carriers was <50%. CONCLUSIONS: Practice-based evaluations of genetic testing in PPGL reveal high mutation detection rates. Although clinical criteria can be used to prioritize mutation testing, mutations were detected in 'low risk groups' indicating a need for comprehensive and inexpensive genetic testing strategies for PPGL and HNPGL.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de Cabeza y Cuello/genética , Paraganglioma/genética , Feocromocitoma/genética , Succinato Deshidrogenasa/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Pruebas Genéticas , Humanos , Persona de Mediana Edad , Estudios Prospectivos
10.
Nat Genet ; 1(4): 295-300, 1992 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1302026

RESUMEN

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant syndrome of unknown aetiology characterized by lifelong elevation in serum calcium concentration and low urinary calcium excretion. These features suggest that the causal gene is important for maintenance of extracellular calcium homeostasis by the parathyroid gland and kidney. To identify the chromosomal location of FHH gene(s), we clinically evaluated 114 individuals in four unrelated affected families and performed linkage analyses. The disease gene mapped to the long arm of chromosome 3 in each family (combined maximum multipoint lod score = 20.67). We suggest that this is the predominant FHH locus and anticipate that identification of the FHH gene will improve our understanding of the molecular basis for physiologic and pathologic regulation of calcium.


Asunto(s)
Calcio/metabolismo , Cromosomas Humanos Par 3 , Ligamiento Genético , Errores Innatos del Metabolismo de los Metales/genética , Secuencia de Bases , Calcio/sangre , Calcio/orina , Bandeo Cromosómico , Mapeo Cromosómico , ADN/sangre , ADN/genética , ADN/aislamiento & purificación , Sondas de ADN , Femenino , Humanos , Escala de Lod , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Linaje , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo Genético
11.
Int J Drug Policy ; : 104111, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37563039

RESUMEN

BACKGROUND: Take home naloxone (THN) programmes are effective at reducing opioid related mortality, but require high levels of distribution, including to the general public. Mass media campaigns can be effective in improving public understanding of a topic and encouraging behavior change. Whilst mass media campaigns focusing on naloxone have been developed internationally, there is a lack of research on their potential impact. We investigated the effects of components of a recent national mass media campaign (Scotland, UK) designed to improve public awareness of drug related deaths, and readiness to intervene. METHODS: We undertook a cross-sectional online experimental study with a randomized design, conducted with a nationally representative sample. Participants (N = 1551; 52.6% female; age 46.1±16.5 years) were assessed on overdose knowledge and readiness to intervene after presentation of eight combinations of campaign components. RESULTS: Compared to a basic campaign description, exposure to all types of campaign component were associated with higher overdose knowledge (p < .001), but not knowledge of what to do in response to an overdose (p = .374), or readiness to intervene (p= .286). The greatest effects were associated with a media rich audio-visual resource (animated video with a popular song on the soundtrack, and narrated by a well-known actor). CONCLUSION: Our data suggest that harm reduction is an appropriate topic for large-scale mass media campaigns. However, effects may be limited to knowledge and awareness raising in the general public, and may be related to the types of media used. Audience segmentation is important and more general messaging about drug related deaths may be more appropriate for the majority of audiences.

12.
Int J Drug Policy ; : 104106, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37563038

RESUMEN

BACKGROUND: Take-home naloxone (THN) programmes have been associated with reductions in opioid-related mortality. In response to high rates of drug-related deaths in Scotland, the Scottish Government commissioned the 'How to save a life' (HTSAL) mass media campaign to: (1) increase awareness of drug-related deaths and how to respond to an overdose, and (2) increase the supply of THN. The aim of this study was to assess the effect of the campaign on the supply of THN. METHODS: We used an interrupted time series design to assess the effect of the HTSAL mass media campaign on the national community supply of THN. The study time period was August 2020-December 2021. We modelled two key dates: the start of the campaign (week beginning (w/b) 30th of August 2021) and after the end of the main campaign (w/b 25th of October 2021). RESULTS: The total number of THN kits distributed in the community in Scotland during the study period was 27,064. The mean number of THN kits distributed per week (relative to the pre-campaign period), increased by 126% during the campaign and 57% post-campaign. In segmented regression analyses, the pre-campaign trend in the number of THN kits supplied was increasing by an average of 1% each week (RR=1.01, 95% CI 1.01 to 1.01, p<0.001). Once the campaign started, a significant change in level was observed, and the number of kits increased by 75% (RR=1.75, 95% CI 1.29 to 2.40, p<0.001). The trend during the campaign was stable (i.e. not increasing or decreasing) but a significant change in level was observed when the campaign ended, and the number of THN kits supplied decreased by 32% (RR=0.68, 95% CI 0.46 to 0.98, p = 0.042). The trend during the post-campaign period was stable. CONCLUSIONS: The HTSAL campaign had a short term, but large and significant impact, on the community supply of THN in Scotland. Mass media campaigns could be combined with other interventions and strategies to maintain the increased uptake of THN outside of campaign periods.

13.
J Hosp Infect ; 135: 125-131, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36996907

RESUMEN

BACKGROUND: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves. AIM: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty. METHODS: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. The association between temperature, heatwaves and SSI was studied using mixed effects logistic regression models fitted at the patient level. Poisson mixed models were fitted for both calendar year and month of the year to investigate the SSI incidence trajectory over time. RESULTS: We included 116,981 procedures performed in 122 hospitals. Significantly higher SSI rates were observed for procedures performed in the summertime (incidence rate ratio 1.39, 95% CI (1.20-1.60), P<0.001; reference: autumn) or in calendar months in which the mean temperature was above 20 °C (reference 5-10 °C; odds ratio 1.59, 95% CI (1.27, 1.98), P<0.001). We observed a slight but non-significant increase in the rate of SSI during heatwaves (1.44% versus 1.01%, P=0.2). CONCLUSION: SSI rates after hip and knee replacement appear to increase with higher environmental temperature. To establish whether, and to what extent, heatwaves increase the risk of SSI, studies involving geographical areas with larger variability in temperature are needed.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Temperatura , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Cadera/efectos adversos , Hospitales
14.
Vaccine ; 41(48): 7183-7191, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37865598

RESUMEN

OBJECTIVE: To describe self-reported reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy. DESIGN: National, prospective cohort study. SETTING: Participants across Canada were enrolled from July 2021 until June 2022. POPULATION: Individuals pregnant during the COVID-19 pandemic, regardless of vaccination status, were included. METHODS: The Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals (COVERED) was advertised through traditional and social media. Surveys were administered at baseline, following each vaccine dose if vaccinated, pregnancy conclusion, and every two months for 14 months. Changes to pregnancy or vaccination status, SARS-CoV-2 infections, or significant health events were recorded. MAIN OUTCOME MEASURES: Reactogenicity (local and systemic adverse events, and serious adverse events) within 1 week post-vaccination, pregnancy and neonatal outcomes, and subsequent SARS-CoV-2 infection. RESULTS: Among 2868 participants who received 1-2 doses of a COVID-19 vaccine during pregnancy, adverse events described included: headache (19.5-33.9%), nausea (4.8-13.8%), fever (2.7-10.2%), and myalgia (33.4-42.2%). Reactogenicity was highest after the 2nd dose of vaccine in pregnancy. Compared to 1660 unvaccinated participants, there were no statistically significant differences in adverse pregnancy or infant outcomes, aside from an increased risk of NICU admission ≥ 24 h among the unvaccinated group. During follow-up, there was a higher rate of participant-reported SARS-CoV-2 infection in the unvaccinated compared to the vaccinated group (18[47.4%] vs. 786[27.3%]). CONCLUSIONS: Participant-reported reactogenicity was similar to reports from non-pregnant adults. There was no increase in adverse pregnancy and birth outcomes among vaccinated vs. unvaccinated participants and lower rates of SARS-CoV-2 infection were reported in vaccinated participants. TWEETABLE ABSTRACT: No significant increase in adverse pregnancy or infant outcomes among vaccinated versus unvaccinated pregnant women in Canada.


Asunto(s)
COVID-19 , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Canadá/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Lactancia , Pandemias , Resultado del Embarazo , Estudios Prospectivos , SARS-CoV-2 , Vacunación/efectos adversos
15.
Clin Endocrinol (Oxf) ; 76(1): 26-32, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21767289

RESUMEN

OBJECTIVE: Patients with primary aldosteronism (PA) who are suitable for surgery should undergo adrenal computerised tomography (CT) and adrenal venous sampling (AVS). A retrospective study was performed of 100 patients with PA. We determined the optimal AVS lateralisation ratio for unilateral disease and reviewed adrenalectomy outcomes evaluating which characteristics predicted hypertension cure. METHODS: AVS was performed in 93 patients. Lateralisation criteria were assessed using ROC curve analysis. The outcome of adrenalectomy was reviewed in 39 patients and predictive factors for cure determined using univariate and multivariate analysis. RESULTS: Of previously published criteria, ROC curve analysis found a cortisol corrected aldosterone affected to unaffected (Aldo/Cort A:U) cut-off of 2·0 was the best predictor of adenoma identifying 80·4% of patients. A novel ratio calculated by dividing the affected to unaffected ratio by the unaffected to peripheral ratio [(Aldo/Cort A:U)/(Aldo/Cort U:IVC)] was successful in identifying 87·0% of patients. Cure rate for blood pressure after adrenalectomy was 38·5% with improvement in 59·0%. On univariate analysis, predictors of post-operative hypertension were increased weight, raised creatinine, left ventricular hypertrophy (LVH) and male sex. On multivariate analysis, male sex and higher pre-operative systolic blood pressure were predictive. CONCLUSIONS: Patients with PA should have CT scanning and AVS. Aldo/Cort A:U >2·0 is the most accurate of previously published ratios in predicting unilateral disease. When patients were carefully selected for surgery, 97% had cure or improvement in blood pressure control. Further confirmatory work is required on a novel ratio which was even more predictive in our series.


Asunto(s)
Adrenalectomía , Presión Sanguínea/fisiología , Hiperaldosteronismo/cirugía , Potasio/metabolismo , Tomografía Computarizada por Rayos X , Femenino , Humanos , Hiperaldosteronismo/sangre , Masculino , Persona de Mediana Edad , Potasio/sangre , Estudios Retrospectivos , Resultado del Tratamiento
16.
Clin Endocrinol (Oxf) ; 77(3): 423-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22420492

RESUMEN

OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.


Asunto(s)
Sulfato de Deshidroepiandrosterona/uso terapéutico , Hipopituitarismo/sangre , Hipopituitarismo/tratamiento farmacológico , Insulina/sangre , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/tratamiento farmacológico , Adulto , Anciano , Glucemia/metabolismo , Estudios Cruzados , Sulfato de Deshidroepiandrosterona/efectos adversos , Método Doble Ciego , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipopituitarismo/complicaciones , Lípidos/sangre , Persona de Mediana Edad , Calidad de Vida
17.
Nature ; 441(7091): 315-21, 2006 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-16710414

RESUMEN

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.


Asunto(s)
Cromosomas Humanos Par 1/genética , Secuencia de Bases , Momento de Replicación del ADN , Enfermedad , Duplicación de Gen , Genes/genética , Variación Genética/genética , Genómica , Humanos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Seudogenes/genética , Recombinación Genética/genética , Selección Genética , Análisis de Secuencia de ADN
18.
Br J Biomed Sci ; 69(3): 126-33, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23057161

RESUMEN

Many drugs have been reported to convert dendritic cells (DCs) into a tolerogenic phenotype in vitro. However, there is evidence that an additional stimulus, such as lipopolysaccharide (LPS), may also be necessary for tolerogenic function in vivo. Little is known concerning the effects of drug modification on LPS-prestimulated DCs. In this study, monocyte-derived immature DCs were stimulated with LPS first and the influence investigated of six different agents on surface antigen expression, cytokine production and lymphocyte proliferation and cytotoxicity. Mycophenolic acid- and rapamycin-exposed DCs had little effect on surface antigen expression or functional activity towards lymphocytes. In contrast, treatment of immature dendritic cells with aspirin, dexamethasone, 1alpha,25-dihydroxyvitamin D3 (VD3) or butyric acid was associated with diminished expression of CD1a, CD1c, CD40, CD80 and CD83. Dendritic cell modification by aspirin, dexamethasone and VD3 were all associated with decreased production of tumour necrosis factor-alpha (TNFalpha). Furthermore, VD3 treatment was associated with a consistent and significant elevation of IL-6 production. Aspirin-, dexamethasone- VD3- and butyric acid-modified DCs suppressed interferon-gamma production, proliferation and cytotoxicity in co-culture with allogeneic mononuclear cells, but inconsistent results were obtained with different allogeneic combinations. Different drugs show varying effects on DC phenotype. No single agent was consistently effective in suppressing the stimulation of allogeneic mononuclear cells and future work is needed to explore drug combinations.


Asunto(s)
Antiinflamatorios/farmacología , Citocinas/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Lipopolisacáridos/farmacología , Monocitos/citología , Monocitos/inmunología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Monocitos/efectos de los fármacos
19.
Int J Drug Policy ; 101: 103547, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34906847

RESUMEN

BACKGROUND: Alcohol marketing helps shape how gender roles and relations are understood, and the gendered nature of drinking learned. In recent years, changes in how women are presented and addressed in marketing, including alcohol marketing, have been observed. This reflects the shifting social, political and regulatory context, in which increased attention has been given to gender inequality and the damaging impact of gender stereotypes. Research is yet to explore the gendered nature of alcohol marketing within this contemporary context. METHODS: A quantitative content and qualitative thematic analysis of alcohol marketing posts (N = 2600) by 20 alcohol brands on Facebook and Instagram pages over an 18 month period (1st January 2019-30th June 2020) was conducted. Marketing strategies were identified, and the way in which posts targeted, represented and engaged women analysed. FINDINGS: New (e.g. 'influencer' collaborations) and established (e.g. competitions) strategies were being used to target both women and men. Drinking was presented as a feminine practice and as an important component of 'doing' a combination of traditional, post-feminist and feminist femininities. Women were assigned a range of gender roles that acknowledged their individual pleasures and achievements, and traditional gender roles and stereotypes were both reinforced and rejected to promote alcohol use. An important move away from sexualising and demeaning women to the appropriation of feminist and equality messages was observed, which may appeal to a wider range of women, including those embracing feminist identities. CONCLUSION: Alcohol brand marketing encourages alcohol use to women through both perpetuating and challenging gender stereotypes. Claims by brands of a commitment to equality are at odds with the harms related to alcohol consumption that contribute to the widening of health and social inequalities. It is important that future work on women's drinking and alcohol marketing is situated within the shifting social-political climate in which traditional, post-feminist and new fourth wave feminist rhetoric and femininities co-exist.


Asunto(s)
Medios de Comunicación Sociales , Femenino , Humanos , Masculino , Mercadotecnía , Factores Socioeconómicos
20.
J Hosp Infect ; 122: 108-114, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35090955

RESUMEN

BACKGROUND: There was a nosocomial outbreak of vancomycin-resistant enterococci (VRE) at the hospital between 1st January 2018 and 31st July 2020. The goals of this study were to describe weekly prevalence, and to identify possible effects of the introduction of selected infection control measures. METHODS: A room-centric analysis of 12 floors (243 rooms) of the main hospital building was undertaken, including data on 37,558 patients over 22,072 person-weeks for the first 2 years of the outbreak (2018-2019). Poisson Bayesian hierarchical models were fitted to estimate prevalence per room and per week, including both spatial and temporal random effects terms. RESULTS: Exploratory data analysis revealed significant variability in prevalence between departments and floors, along with sporadic spatial and temporal clustering during colonization 'flare-ups'. The oncology department experienced slightly higher prevalence over the 104-week study period [adjusted prevalence ratio (aPR) 4.8, 95% confidence interval (CI) 2.6-8.9; P<0.001; compared with general medicine], as did both the cardiac surgery (aPR 3.8, 95% CI 2.0-7.3; P<0.001) and abdominal surgery (aPR 3.7, 95% CI 1.8-7.6; P<0.001) departments. Estimated peak prevalence was reached in July 2018, at which point a number of new infection control measures (including the daily disinfection of rooms and room cleaning with ultraviolet light upon patient discharge) were introduced that resulted in decreasing prevalence (aPR 0.89 per week, 95% CI 0.87-0.91; P<0.001). CONCLUSION: Relatively straightforward but personnel-intensive cleaning with disinfectants and ultraviolet light provided tangible benefits in getting the outbreak under control. Despite additional complexity, Bayesian hierarchical models provide a more flexible platform to study transmission dynamics.


Asunto(s)
Infección Hospitalaria , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Teorema de Bayes , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/prevención & control , Humanos , Prevalencia , Centros de Atención Terciaria
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