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1.
J Cancer Educ ; 2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35112296

RESUMEN

Ideal efforts for cancer prevention would include lifestyle modifications along with routine, age-eligible cancer screening. Employing an asset-based approach within vulnerable populations already engaging in at least one healthy behavior (i.e., physical activity) may be an ideal way to further reduce cancer risk across peer groups with low cancer screening rates. Guided by the theory of planned behavior (TPB), the aim of this study was to identify constructs associated with cancer screening intentions among young to middle aged adults for influencing educational and behavioral interventions designed to promote cancer prevention. A cross-sectional, web-based survey was utilized to assess attitudes, subjective norms, perceived behavioral control, and intention to screen for cancer among physically active adults aged 18-49 years. Descriptive and bivariate analyses were conducted to characterize the sample, and hierarchical linear regression analyses were conducted to assess the influence of sociodemographic variables and TPB constructs on cancer screening intentions. Age, female sex, reporting a routine doctor's visit, reported knowledge of physical activity as a lifestyle behavior to reduce cancer risk, and an increased number of motivating factors for engaging in physical activity were significantly associated with higher cancer screening intention (P < 0.001). With the addition of TPB constructs (i.e., subjective norms and perceived behavioral control), the final analytic model accounted for 31% of the variance in intention to screen for cancer. Findings suggest that the TPB could be used to tailor or design asset-based, cancer education interventions to effectively promote age-eligible cancer screenings among physically active adults. Educational content to increase social support for cancer screening and enhance perceived behavioral control to complete screening is essential in this population.

2.
NPJ Aging Mech Dis ; 7(1): 14, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34210964

RESUMEN

To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (ntotal = 75,666, nwomen = 47,700, nmen = 27,966; ages 18-85 years old, mean (M)Age = 46.54, standard deviation (SD)Age = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (ntotal = 158,249 nwomen = 89,333 nmen = 68,916; ages 40-70 years old, MAge = 55.81, SDAge = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (ntotal = 39,795, nwomen = 29,640, nmen = 10,155; ages 40-70 years old, MAge = 56.59, SDAge = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.

3.
Sci Rep ; 11(1): 10248, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33986309

RESUMEN

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.


Asunto(s)
Fumar Cigarrillos/efectos adversos , Memoria/efectos de los fármacos , Aprendizaje Verbal/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Fumar Cigarrillos/psicología , Cognición/efectos de los fármacos , Cognición/fisiología , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Demencia Vascular/etiología , Femenino , Humanos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Factores Sexuales , Aprendizaje Verbal/fisiología
4.
J Laryngol Otol ; 134(6): 519-525, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32613920

RESUMEN

OBJECTIVE: To present our data evaluating the feasibility of simultaneous cochlear implantation with resection of acoustic neuroma. METHODS: This paper describes a case series of eight adult patients with a radiologically suspected acoustic neuroma, treated at a tertiary referral centre in Newcastle, Australia, between 2012 and 2015. Patients underwent cochlear implantation concurrently with removal of an acoustic neuroma. The approach was translabyrinthine, with facial nerve monitoring and electrically evoked auditory brainstem response testing. Standard post-implant rehabilitation was employed, with three and six months' follow-up data collected. The main outcome measures were: hearing, subjective benefit of implant, operative complications and tumour recurrence. RESULTS: Eight patients underwent simultaneous cochlear implantation with resection of acoustic neuroma over a 3-year period, and had 25-63 months' follow up. There were no major complications. All patients except one gained usable hearing and were daily implant users. CONCLUSION: Simultaneous cochlear implantation with resection of acoustic neuroma has been shown to be a safe treatment option, which will be applicable in a wide range of clinical scenarios as the indications for cochlear implantation continue to expand.


Asunto(s)
Implantación Coclear/métodos , Terapia Combinada/métodos , Audición/fisiología , Neuroma Acústico/cirugía , Adolescente , Anciano , Australia/epidemiología , Terapia Combinada/estadística & datos numéricos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Nervio Facial/cirugía , Estudios de Factibilidad , Estudios de Seguimiento , Pruebas Auditivas/métodos , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/patología , Neuroma Acústico/rehabilitación , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del Tratamiento
5.
Mol Psychiatry ; 23(3): 759-766, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28607458

RESUMEN

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.


Asunto(s)
Trastorno del Espectro Autista/etiología , Trastorno Autístico/etiología , Adulto , Femenino , Fiebre/complicaciones , Ligamiento Genético , Edad Gestacional , Humanos , Inmunidad Innata/inmunología , Lactante , Recién Nacido , Infecciones/complicaciones , Masculino , Exposición Materna , Madres , Noruega , Oportunidad Relativa , Embarazo , Segundo Trimestre del Embarazo/fisiología , Efectos Tardíos de la Exposición Prenatal , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Encuestas y Cuestionarios
6.
QJM ; 111(4): 267-268, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29149277
7.
Science ; 355(6325)2017 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-28183913

RESUMEN

The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radical enzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and human pathogens to dehydrate trans-4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities.


Asunto(s)
Microbioma Gastrointestinal/genética , Tracto Gastrointestinal/microbiología , Hidroxiprolina/metabolismo , Prolina Oxidasa/química , Prolina Oxidasa/genética , Secuencias de Aminoácidos , Anaerobiosis , Humanos , Metagenoma , Prolina Oxidasa/metabolismo , Propanodiol Deshidratasa/química , Propanodiol Deshidratasa/genética , Procesamiento Proteico-Postraduccional , Alineación de Secuencia
8.
Maturitas ; 92: 115-122, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27621248

RESUMEN

OBJECTIVE: To examine whether or not cigarette smoking, alcohol and caffeine intake are related to two indicators of ovarian age-anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH). STUDY DESIGN: Cross-sectional study of 477 women with a recent index spontaneous abortion (SA) (105 trisomic, 93 non-trisomic) or livebirth (LB) (279) with hormones measured on days 2-4 of an apparently normal menstrual cycle after the index pregnancy. RESULTS: Current smoking is associated with about a 15% increase in median FSH (ß for ln(FSH)=0.14, 95% CI 0.03,0.25). It is not significantly related to AMH (ß for ln(AMH)=-0.25, 95% CI -0.56,0.06). Neither alcohol 2-7days per week nor caffeine 122-<553mg per day is independently related to AMH or FSH. CONCLUSIONS: The observation that current smoking is associated with FSH, but not with AMH, suggests that current smoking either impairs the development of antral follicles or dysregulates the hypothalamic-pituitary-ovarian axis. The absence of an association with AMH argues against mechanisms related to accelerated follicle atresia.


Asunto(s)
Consumo de Bebidas Alcohólicas/fisiopatología , Hormona Antimülleriana/sangre , Cafeína/farmacología , Hormona Folículo Estimulante/sangre , Ovario/fisiología , Fumar/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Folículo Ovárico , Ovario/efectos de los fármacos , Embarazo , Reproducción , Adulto Joven
9.
Dokl Biochem Biophys ; 467(1): 124-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27193715

RESUMEN

A pronounced pleiotropic effect of thyroid hormones on the regulation of gene expression in fish in postembryogenesis was demonstrated for the first time using larvae and juveniles of the blue bream Ballerus ballerus as an example. Genome-wide transcriptome sequencing (RNA-seq) identified 1212 differentially expressed genes in the brain and liver of fish kept in triiodothyronine solution (0.25 ng/mL). Our data show that the regulation of gene expression by thyroid hormones is widespread in nature: it involves not only the structural genes but also the regulatory genes. A significant number of genes under the control of thyroid hormones are involved in the determination of morphological traits.


Asunto(s)
Cyprinidae/crecimiento & desarrollo , Cyprinidae/metabolismo , Expresión Génica/fisiología , Hormonas Tiroideas/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Proteínas de Peces/metabolismo , Perfilación de la Expresión Génica , Ontología de Genes , Larva , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Hormonas Tiroideas/administración & dosificación , Transcriptoma/fisiología , Triyodotironina/administración & dosificación
10.
Am J Transplant ; 15(10): 2691-703, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25988811

RESUMEN

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.


Asunto(s)
Rechazo de Injerto/inmunología , Enfermedad Injerto contra Huésped/inmunología , Intestinos/trasplante , Trasplante de Hígado , Linfocitos T/inmunología , Quimera por Trasplante/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Citometría de Flujo , Estudios de Seguimiento , Rechazo de Injerto/sangre , Enfermedad Injerto contra Huésped/sangre , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Quimera por Trasplante/sangre , Adulto Joven
11.
Zh Evol Biokhim Fiziol ; 51(1): 17-20, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-25859601

RESUMEN

The activity of hydrolases (maltase, saccharase, amylolytic activity) in the intestinal mucosa of the plankton-feeding zope Ballerus ballerus and the benthos-feeding white-eye bream Ballerus sapa was investigated. The temperature characteristics of maltase hydrolysis (T(opt) and E(act)) are similar in both species. The lower K(m) of maltase hydrolysis in the white-eye bream reflects a higher enzyme/substrate affinity and indicates a more effective carbohydrate hydrolysis in the benthos-versus plankton-feeding species. The glycosidase activity in the white-eye bream is twice as high as in the zope. This may be due not only to different feeding spectra and biochemical food contents but also to the differences in thyroid status of species under consideration.


Asunto(s)
Cyprinidae/metabolismo , Proteínas de Peces , Glicósido Hidrolasas , Mucosa Intestinal/enzimología , Animales , Conducta Alimentaria , Proteínas de Peces/química , Proteínas de Peces/aislamiento & purificación , Proteínas de Peces/metabolismo , Glicósido Hidrolasas/química , Glicósido Hidrolasas/aislamiento & purificación , Glicósido Hidrolasas/metabolismo , Plancton
12.
Diabetes Obes Metab ; 16 Suppl 1: 49-55, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25200296

RESUMEN

Fatty acid (FA)-sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as insulin secretion and action. Subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Molecular effectors of these FA effects probably include chloride or potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K⁺ channel appear to be necessary for some of the signalling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, an FA transporter/receptor that does not require intracellular metabolism to activate downstream signalling. Thus, FA or their metabolites can modulate neuronal activity as a means of directly monitoring ongoing fuel availability by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Recently, the role of lipoprotein lipase in FA sensing has also been shown in animal models not only in hypothalamus, but also in hippocampus and striatum. Finally, FA overload might impair neural control of energy homeostasis through enhanced ceramide synthesis and may contribute to obesity and/or type 2 diabetes pathogenesis in predisposed subjects.


Asunto(s)
Antígenos CD36/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Retroalimentación Fisiológica , Metabolismo de los Lípidos , Modelos Neurológicos , Neuronas/metabolismo , Núcleo Hipotalámico Ventromedial/metabolismo , Animales , Regulación del Apetito , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Ácidos Grasos no Esterificados/sangre , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Lipoproteína Lipasa/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Especificidad de Órganos , Núcleo Hipotalámico Ventromedial/citología
13.
Am J Transplant ; 14(7): 1581-91, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24935695

RESUMEN

Preexisting serum antibodies have long been associated with graft loss in transplant recipients. While most studies have focused on HLA-specific antibodies, the contribution of non-HLA-reactive antibodies has been largely overlooked. We have recently characterized mAbs secreted by B cell clones derived from kidney allograft recipients with rejection that bind to apoptotic cells. Here, we assessed the presence of such antibodies in pretransplant serum from 300 kidney transplant recipients and examined their contribution to the graft outcomes. Kaplan-Meier survival analysis revealed that patients with high pretransplant IgG reactivity to apoptotic cells had a significantly increased rate of late graft loss. The effect was only apparent after approximately 1 year posttransplant. Moreover, the association between pretransplant IgG reactivity to apoptotic cells and graft loss was still significant after excluding patients with high reactivity to HLA. This reactivity was almost exclusively mediated by IgG1 and IgG3 with complement fixing and activating properties. Overall, our findings support the view that IgG reactive to apoptotic cells contribute to presensitization. Taking these antibodies into consideration alongside anti-HLA antibodies during candidate evaluation would likely improve the transplant risk assessment.


Asunto(s)
Apoptosis/inmunología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Antígenos de Histocompatibilidad Clase I/inmunología , Inmunoglobulina G/sangre , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/efectos adversos , Aloinjertos , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/mortalidad , Humanos , Células Jurkat , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia
14.
Diabetes Metab ; 40(1): 29-33, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24210646

RESUMEN

Nutrient-sensitive neurons [to glucose and fatty acids (FAs)] are present at many sites throughout the brain, including the hypothalamus and brain stem, and play a key role in the neural control of energy and glucose homoeostasis. Through their neuronal output, FAs can modulate feeding behaviour as well as insulin secretion and activity. Central administration of oleate, for example, inhibits food intake and glucose production in rats. This suggests that daily variations in plasma FA concentrations could be detected by the central nervous system as a signal that contributes to regulation of energy balance. At the cellular level, subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FAs. Possible molecular effectors of these FA effects most likely include the chloride and potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K(+) channels appear to be necessary for some signalling effects of FAs, at least half the FA responses in ventromedial hypothalamic neurons are mediated by interaction with fatty acid translocase (FAT)/CD36, an FA transporter/receptor that does not require intracellular metabolism to activate downstream signalling. Thus, FAs and their metabolites can modulate neuronal activity by directly monitoring the ongoing fuel availability for brain nutrient-sensing neurons involved in the regulation of energy and glucose homoeostasis. Besides these physiological effects, FA overload or metabolic dysfunction may also impair neural control of energy homoeostasis and contribute to obesity and/or type 2 diabetes in predisposed subjects.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Grasos/metabolismo , Conducta Alimentaria , Hipotálamo/metabolismo , Neuronas/metabolismo , Obesidad/metabolismo , Ingestión de Alimentos , Metabolismo Energético , Femenino , Predisposición Genética a la Enfermedad , Homeostasis , Humanos , Hipotálamo/fisiología , Canales KATP/metabolismo , Metabolismo de los Lípidos , Masculino , Canales de Potasio/metabolismo , Transducción de Señal
15.
Int J Obes (Lond) ; 37(12): 1515-23, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23478425

RESUMEN

OBJECTIVE: Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to have a role in obesity risk. The present study tested the hypothesis that (i) the microstructure of chronic high-fat diet intake differs between genetically selected diet-induced obesity (DIO) and diet-resistant (DR) rats, and (ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. DESIGN: Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). RESULTS: Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ∼40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with two-third less water. CONCLUSIONS: Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically prone DIO rats, which otherwise show a 'gorging' meal pattern. These results open new opportunities of investigation toward treating some forms of DIO.


Asunto(s)
Depresores del Apetito/farmacología , Grasas de la Dieta/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Obesidad/tratamiento farmacológico , Urocortinas/farmacología , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Conducta Animal , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Ingestión de Líquidos/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Obesidad/etiología , Obesidad/prevención & control , Ratas , Ratas Mutantes , Factores de Tiempo
16.
J Laryngol Otol ; 127 Suppl 1: S13-20, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22892109

RESUMEN

BACKGROUND: Chronic tympanic membrane perforations can cause significant morbidity. The term myringoplasty describes the operation used to close such perforations. A variety of graft materials are available for use in myringoplasty, but all have limitations and few studies report post-operative hearing outcomes. Recently, the biomedical applications of silk fibroin protein have been studied. This material's biocompatibility, biodegradability and ability to act as a scaffold to support cell growth prompted an investigation of its interaction with human tympanic membrane keratinocytes. METHODS AND MATERIALS: Silk fibroin membranes were prepared and human tympanic membrane keratinocytes cultured. Keratinocytes were seeded onto the membranes and immunostained for a number of relevant protein markers relating to cell proliferation, adhesion and specific epithelial differentiation. RESULTS: The silk fibroin scaffolds successfully supported the growth and adhesion of keratinocytes, whilst also maintaining their cell lineage. CONCLUSION: The properties of silk fibroin make it an attractive option for further research, as a potential alternative graft in myringoplasty.


Asunto(s)
Fibroínas , Queratinocitos/fisiología , Miringoplastia/métodos , Andamios del Tejido , Perforación de la Membrana Timpánica/cirugía , Membrana Timpánica/citología , Adulto , Materiales Biocompatibles , Técnicas de Cultivo de Célula , Proliferación Celular , Niño , Enfermedad Crónica , Técnica del Anticuerpo Fluorescente , Humanos , Queratinocitos/metabolismo , Queratinocitos/ultraestructura , Ensayo de Materiales/métodos , Proteínas de la Membrana/metabolismo , Otitis Media Supurativa/complicaciones , Proteína Proto-Oncogénica c-ets-1/metabolismo , Ingeniería de Tejidos/métodos , Membrana Timpánica/fisiología , Perforación de la Membrana Timpánica/complicaciones
17.
J Laryngol Otol ; 127 Suppl 1: S30-4, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23186827

RESUMEN

BACKGROUND: Streptococcus pneumoniae is a frequent cause of acute mastoiditis. Despite the recent (2005) introduction of pneumococcal vaccination, mastoiditis incidence and severity may be increasing. This study aimed to assess the incidence, severity and microbiology of acute mastoiditis over an 11-year period. METHODS: Retrospective review of paediatric acute mastoiditis cases seen at our institution (2000-2010), comparing patients seen prior to vaccination introduction (period one, 2000-2004), around the time of vaccine introduction (period two, 2005-2007) and post-vaccination (period three, 2008-2010). RESULTS: We reviewed 84 children. In periods one, two and three, respectively: mean annual case load was 8.4, 5 and 9 children; pneumococcal isolates were seen in 40.5, 6.7 and 29.6 per cent of cases; highest recorded fever was 38.6, 38.9 and 38.2°C and highest leukocyte count 18.9, 15.0 and 15.6 × 109/l; incidence of intracranial complications was 11.9, 0 and 7.4 per cent; mean duration of intravenous antibiotics was 6.0, 4.1 and 4.2 days; proportion treated surgically was 71.4, 60.0 and 48.1 per cent; and mean length of in-patient stay shortened. CONCLUSION: Pneumococcal mastoiditis admission rates appeared to fall when vaccination was introduced, with concomitant reduction in overall mastoiditis incidence and intracranial complications; subsequently, however, admission rates rapidly returned to pre-vaccination levels.


Asunto(s)
Mastoiditis/prevención & control , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Índice de Severidad de la Enfermedad , Streptococcus pneumoniae/aislamiento & purificación , Vacunación , Enfermedad Aguda , Administración Intravenosa , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Preescolar , Femenino , Fiebre/epidemiología , Hospitalización/tendencias , Humanos , Incidencia , Lactante , Recuento de Leucocitos/estadística & datos numéricos , Masculino , Mastoiditis/epidemiología , Mastoiditis/microbiología , Nueva Gales del Sur/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Estudios Retrospectivos
18.
Cancer Gene Ther ; 19(11): 757-66, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22956041

RESUMEN

Sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. However, their efficacy against blood cancer has not been well established. Here, we show that Sindbis vectors infect and efficiently trigger apoptosis in mouse BW5147 malignant hematopoietic T-cells, but only at low levels in human lymphoma and leukemia cells (Jurkat, Karpas, CEM, DHL and JB). The Mr 37/67 kD laminin receptor (LAMR) has been suggested to be the receptor for Sindbis virus. However, JB cells, which are infected by Sindbis at low efficiency, express high levels of LAMR, revealing that additional factors are involved in Sindbis tropism. To test the infectivity and therapeutic efficacy of Sindbis vectors against malignant hematopoietic cells in vivo, we injected BW5147 cells intraperitoneally into (C3HXAKR) F1 hybrid mice. We found that Sindbis vectors targeted the tumors and significantly prolonged survival of tumor-bearing mice. We also tested the Sindbis vectors in a transgenic CD4-Rgr model, which spontaneously develop thymic lymphomas. However, infectivity in this model was less efficient. Taken together, these results demonstrate that Sindbis vectors have the potential to target and kill hematopoietic malignancies in mice, but further research is needed to evaluate the mechanism underlining the susceptibility of human lymphoid malignancies to Sindbis therapy.


Asunto(s)
Vectores Genéticos/metabolismo , Neoplasias Hematológicas/metabolismo , Neoplasias Experimentales/terapia , Viroterapia Oncolítica , Virus Sindbis/metabolismo , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/metabolismo , Apoptosis , Femenino , Regulación Neoplásica de la Expresión Génica , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Neoplasias Hematológicas/terapia , Humanos , Inyecciones Intraperitoneales , Células Jurkat , Masculino , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C3H , Ratones Transgénicos , Metástasis de la Neoplasia , Receptores de Laminina/genética , Receptores de Laminina/metabolismo , Virus Sindbis/genética , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/farmacología
20.
Hum Reprod ; 27(7): 2224-32, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22493044

RESUMEN

BACKGROUND: We hypothesized that trisomy arises as a function of the size of the oocyte pool, with risk increased among women with diminished pools. Diminished pools may cause primary ovarian failure, which has been associated with premutation and intermediate CGG repeat length at the Fragile X mental retardation (FMR1) locus. Thus, we hypothesized that the risk of trisomic pregnancy is increased among women with intermediate CGG repeat length on the FMR1 gene. METHODS: The analysis drew on data from two hospital-based case-control studies. We compared 207 women with trisomic spontaneous abortions (SAs) to three comparison groups: 82 women with other chromosomally abnormal SAs, 99 women with chromosomally normal SAs and 537 women with live births (LBs), age matched to women with SAs. We defined the length of the CGG repeat in four ways: the biallelic mean, the genotypic mean, the length on allele 2 and the length on allele 1. We analyzed CGG repeat length as a categorical variable. All analyses were adjusted for site, age and ethnicity. RESULTS: CGG repeat length did not differ significantly between women with trisomic SAs and any of the three comparison groups. For the biallelic mean, the adjusted odds ratio relating trisomy (versus LB controls) to the highest category (35.5-59.5 repeats) versus the modal category (26.5-30.0 repeats) was 1.5 (95% confidence interval (CI): 0.7, 3.1). Comparisons with the two SA control groups also showed increased odds of more repeats among trisomy cases. Results were similar when repeat length was defined by the genotypic mean or by the repeat length on allele 2. For allele 1, the odds of short (9-19) repeat length were lower, but not significantly so, for trisomy cases compared with LB controls. Excluding women with premutations (n= 2) from the analysis yielded an adjusted odds ratio of 1.4 (95% CI: 0.7, 2.9) for the biallelic mean. CONCLUSIONS: Our data are equivocal. The direction of associations is consistent with the hypothesis that repeat length in the intermediate range is associated with trisomy. However, differences between the trisomy cases and the comparison groups are neither large nor statistically significant. Our data rule out odds ratios larger than about 3.


Asunto(s)
Proteína del Retraso Mental del Síndrome del Cromosoma X Frágil/genética , Oocitos/citología , Expansión de Repetición de Trinucleótido/genética , Trisomía/genética , Aborto Espontáneo/genética , Alelos , Aneuploidia , Estudios de Casos y Controles , Mapeo Cromosómico/métodos , Femenino , Síndrome del Cromosoma X Frágil/genética , Genotipo , Humanos , Mutación , Oportunidad Relativa , Embarazo , Riesgo
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