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OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.
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COVID-19/prevención & control , Colposcopía/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Frotis Vaginal/estadística & datos numéricos , Adulto , Anciano , Bases de Datos Factuales , Atención a la Salud/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Ontario , SARS-CoV-2 , Adulto JovenRESUMEN
Band inversions are key to stabilising a variety of novel electronic states in solids, from topological surface states to the formation of symmetry-protected three-dimensional Dirac and Weyl points and nodal-line semimetals. Here, we create a band inversion not of bulk states, but rather between manifolds of surface states. We realise this by aliovalent substitution of Nb for Zr and Sb for S in the ZrSiS family of nonsymmorphic semimetals. Using angle-resolved photoemission and density-functional theory, we show how two pairs of surface states, known from ZrSiS, are driven to intersect each other near the Fermi level in NbGeSb, and to develop pronounced spin splittings. We demonstrate how mirror symmetry leads to protected crossing points in the resulting spin-orbital entangled surface band structure, thereby stabilising surface state analogues of three-dimensional Weyl points. More generally, our observations suggest new opportunities for engineering topologically and symmetry-protected states via band inversions of surface states.
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BACKGROUND: Leisure activities can be both enjoyable and cognitively stimulating, and participation in such activities has been associated with reduced age-related cognitive decline. Thus, integrating stimulating leisure activities in cognitive training programs may represent a powerful and innovative approach to promote cognition in older adults at risk of dementia. The ENGAGE study is a randomized controlled, double-blind preference trial with a comprehensive cohort design that will test the efficacy and long-term impact of an intervention that combines cognitive training and cognitively stimulating leisure activities. METHODS: One hundred and forty-four older adults with a memory complaint will be recruited in Montreal and Toronto. A particular effort will be made to reach persons with low cognitive reserve. Participants will be randomly assigned to one of two conditions: cognitive + leisure training (ENGAGE-MUSIC/SPANISH) or active control (ENGAGE-DISCOVERY). The ENGAGE-MUSIC/SPANISH training will include teaching of mnemonic and attentional control strategies, casual videogames selected to train attention, and classes in music or Spanish as a second language. The ENGAGE-DISCOVERY condition will comprise psychoeducation on cognition and the brain, low-stimulating casual videogames and documentary viewing with discussions. To retain the leisure aspect of the activities, participants will be allowed to exclude either music or Spanish at study entry if they strongly dislike one of these activities. Participants randomized to ENGAGE-MUSIC/SPANISH who did not exclude any activity will be assigned to music or Spanish based on a second random assignment. Training will be provided in 24 2-h sessions over 4 months. Outcomes will be measured at baseline, at 4-month follow-up, and at 24-month follow-up. The primary outcome will be cognitive performance on a composite measure of episodic memory (delayed recall scores for words and face-name associations) measured at baseline and at the 4-month follow-up. Secondary outcomes will include a composite measure of attention (speed of processing, inhibition, dual tasking, and shifting), psychological health, activities of daily living, and brain structure and function and long-term maintenance measured at the 24-month follow-up. Information on cognitive reserve proxies (education and lifestyle questionnaires), sex and genotype (apolipoprotein (Apo)E4, brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT)) will be collected and considered as moderators of training efficacy. DISCUSSION: This study will test whether a program combining cognitive training with stimulating leisure activities can increase cognition and reduce cognitive decline in persons at risk of dementia. TRIAL REGISTRATION: NCT03271190 . Registered on 5 September 2017.
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Cognición , Actividades Recreativas , Trastornos de la Memoria/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Atención , Encéfalo/patología , Encéfalo/fisiopatología , Estudios de Cohortes , Método Doble Ciego , Humanos , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Proyectos de InvestigaciónRESUMEN
BACKGROUND & AIMS: Given the enormous health, economic and societal consequences of the obesity pandemic, identifying effective primary prevention strategies represents a global priority. The aim of this study was to provide evidence on the association between adherence to a food-based score reflecting a set of targeted, well-informed, simple dietary recommendations and the incidence of overweight/obesity. METHODS: A total of 11,349 initially free of overweight/obesity young adults (mean [SD] age: 34.7 y [10.7]), were followed up biennially during a median of 9.3 years. The Dietary Obesity-Prevention Score (DOS) was created based on a priori evidence of foods associated with weight changes. The DOS positively weighted the consumption of vegetables, fruits, legumes, yogurt, nuts, fish, and a ratio of vegetable to animal protein; whereas the consumption of red meat, processed meat, saturated animal fat, refined grains, ultra-processed food, sugary beverages, beer and spirits were inversely weighted. Energy-adjusted tertiles of each item were used to build the DOS, ranging from 14 (lowest adherence) to 42 points (highest adherence). Adherence to the DOS was calculated at baseline and after 10 years of follow-up. We assessed both incident overweight/obesity (BMI ≥25 kg/m2) and average yearly weight changes in grams per year (g/y). RESULTS: During 104,887 person-years, 2153 incident cases of overweight/obesity were identified. A higher adherence to the DOS at baseline was significantly associated with lower risk of future development of overweight/obesity [multivariable-adjusted HR (95% CI) for the highest vs. lowest quintile = 0.63 (0.54-0.74)], with a significant linear dose-response relationship (p for trend < 0.001). When the analyses were updated with repeated measures, the results were similar and remained statistically significant. Consistently, increases in average yearly weight gain were significantly lower with better adherence to the DOS. CONCLUSIONS: In this Mediterranean cohort of university graduates, a higher adherence to a food-based score was significantly associated with lower risk of overweight/obesity and lower average annual weight gain. These findings may help counsel patients regarding dietary risks and raise awareness of weight gain before the onset of overweight/obesity.
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Dieta/estadística & datos numéricos , Obesidad/epidemiología , Sobrepeso/epidemiología , Adulto , Encuestas sobre Dietas , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad/prevención & control , Sobrepeso/prevención & control , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: In the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. METHODS: All women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. RESULTS: Of 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p=0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p=0.032) while the time to genetic counseling decreased (p=0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. CONCLUSIONS: Despite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.
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Cistadenocarcinoma Seroso/genética , Asesoramiento Genético , Neoplasias Ováricas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Modelos Logísticos , Persona de Mediana Edad , Derivación y ConsultaRESUMEN
Arising from studies on the amnesia that follows site-specific physical or chemical lesions, the acquisition and consolidation of certain behavioral tasks has been demonstrated to be associated with different hippocampal subregions. Although not absolute, spatial learning is reliant on the dorsal region of the hippocampus, whereas avoidance- and fear-conditioning tasks appear to be dependent on its more ventral aspects. Thus, if learning-associated synapse remodeling is a true feature of memory consolidation it must also follow these regional dissociations. We therefore determined if the learning-associated increases in synapse density that occur in the mid-molecular layer of the dentate gyrus at the 6-h post-training time and the frequency of polysialylated cells at the infragranular zone that occur at the 12-h post-training time were dissociated to specific hippocampal subregions following training in either a massed water maze task or light-dark passive avoidance response. Synapse remodeling was found to occur only in the dorsal hippocampus following spatial learning. We could not, however, discern any regional dissociation of neural remodeling following avoidance conditioning. These results point to strong associations between learning and specific groups of novel synapses during consolidation of spatial learning and avoidance conditioning paradigms.
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Giro Dentado/ultraestructura , Memoria/fisiología , Plasticidad Neuronal/fisiología , Sinapsis/ultraestructura , Animales , Giro Dentado/fisiología , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Aprendizaje/fisiología , Masculino , Microscopía Electrónica de Transmisión , Ratas , Ratas WistarRESUMEN
A growing body of observational research suggests that dairy consumption may have a beneficial effect on the metabolic syndrome (MetS). MetS is a clustering of cardiometabolic risk factors within an individual that carries with it an increased risk of developing cardiovascular disease. A systematic search of electronic databases identified cross-sectional studies (n = 10) and prospective cohort studies (n = 3) that assessed dairy intake in relation to MetS. The quality of the included studies was assessed based on study methodology, measurement and reporting of dietary intake, use of standardized MetS diagnostic criteria and statistical analysis. Dairy intake was inversely associated with incidence or prevalence of MetS in seven out of 13 studies. Three studies found no association between dairy and MetS. Three studies reported mixed relationships between specific dairy foods and MetS. The majority of studies suggested a potential benefit of dairy consumption on the risk of having MetS, but methodological differences, potential biases and other limitations in the studies conducted prevent conclusions to be drawn. Future randomized controlled trials are needed to confirm the effect of dairy consumption on MetS.
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Productos Lácteos , Síndrome Metabólico/epidemiología , Obesidad/epidemiología , Productos Lácteos/efectos adversos , Encuestas Epidemiológicas , Humanos , Síndrome Metabólico/etiología , Síndrome Metabólico/prevención & control , Encuestas Nutricionales , Prevalencia , Factores de RiesgoRESUMEN
OBJECTIVE: There are no evidence based guidelines for the diagnosis of epithelial ovarian cancer (EOC) prior to the initiation of neoadjuvant chemotherapy. The aim of this study was to review our diagnostic practice, provide guidelines for clinical practice, and suggest a diagnostic strategy for validation in future prospective trials. PATIENTS AND METHODS: A retrospective chart review of patients undergoing neoadjuvant chemotherapy followed by debulking surgery was performed. Final diagnoses were based on expert pathology review of surgical specimens. Diagnostic strategies were defined as histologic, cytologic and clinical. Performance of these strategies in predicting final pathology was compared. RESULTS: Between 1994 and 2007, 149 patients were identified. Initial diagnosis was made on the basis of: cytology (paracentesis, thoracentesis, or fine needle aspirate) 72% (108 patients); histology (core biopsy, surgery) 18% (26), clinical (Radiology and CA-125) 10% (15). The final diagnosis was consistent with invasive EOC in 96% of patients. The diagnostic accuracies of the 3 strategies were: cytology 98%, histology 92%, and clinical 87%, (p=0.04). Specific EOC subtype was identified in 59% of patients (histology 77% and cytology 55%). When available, the initial subtype corresponded to the final subtype in 85% of cases: histology 80%, cytology 86%. CONCLUSION: Diagnosis of epithelial ovarian cancer based on cytology and histology are superior to clinical factors alone. In a centre with trained gynecologic cytopathologists, a diagnosis of EOC by cytology is not significantly inferior to a diagnosis made by histology. These data are important for clinical practice and the design of future clinical trials.
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Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Quimioterapia Adyuvante , Células Epiteliales/patología , Medicina Basada en la Evidencia , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Guías de Práctica Clínica como Asunto , Estudios RetrospectivosRESUMEN
As the pathophysiological mechanism(s) of many neuropsychiatric disorders relate to GABAergic interneuron structure and function, we employed isolation rearing of Wistar rats as a model to correlate developmental emergence of cognitive deficits with the expression of reelin-producing interneurons in the medial prefrontal cortex (PFC). Prepulse inhibition deficits emerged at postnatal day 60 and persisted into adulthood. Paralleling the emergence of these neurobehavioural deficits was an increase in reelin production and reelin-immunopositive cells in layer I of the PFC and this later became significantly reduced at postnatal day 80. Cells expressing reelin immunoreactivity in a horizontal orientation were mainly located to the upper regions of layer I whereas those with a vertical orientation, whose arbors extend into cortical layers II and III, were more numerous in the lower regions of layer I and became significantly dysregulated during postnatal development. No behavioural deficits or altered reelin expression was observed at postnatal days 30 or 40. Developmental emergence of neurobehavioural and reelin deficits in isolation reared animals is proposed to reflect maladaptive wiring within the medial prefrontal cortex during a critical maturation period of this circuitry.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Interneuronas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Corteza Prefrontal/metabolismo , Filtrado Sensorial/fisiología , Serina Endopeptidasas/metabolismo , Aislamiento Social , Animales , Conducta Animal/fisiología , Western Blotting , Recuento de Células , Vivienda para Animales , Masculino , Actividad Motora/fisiología , Red Nerviosa/metabolismo , Ratas , Ratas Wistar , Proteína Reelina , Reflejo de Sobresalto/fisiologíaRESUMEN
Processing of information for long-term storage requires specific patterns of activity that lead to modification of synapse structure and eventual change in neural connectivity pattern. Morphological change associated with memory consolidation is reliant on neural cell adhesion molecule (NCAM) function and that of its polysialylated variant (NCAM PSA). Across species and paradigms, a transient frequency increase of polysialylated neurons in the hippocampal dentate has been found necessary for memory consolidation, however, recent studies suggest that NCAM PSA may serve to suppress memory formation in certain paradigms. As intraventricular infusions of NCAM blocking antibodies have been used successfully to demonstrate its time-dependent role at the 6 h post-training period of memory consolidation, we employed the same procedure to demonstrate a functional requirement for NCAM PSA in the consolidation of two commonly used behavioral paradigms: avoidance conditioning and spatial learning in Wistar rats. Anti-PSA was found to significantly induce amnesia of the passive avoidance response when infused at the 10 h post-training time, a period coincident with the learning-associated increase in dentate polysialylated cell frequency. Moreover, the amnesia became apparent at the 48 h recall time and was not apparent at the 24 h post-training time, suggesting a possible role in memory reconsolidation. A similar anti-PSA action was observed following water maze training in aged animals but was not apparent in young animals, an effect suggested to be due to inadequate antibody saturation of the polysialylated cell population. These studies confirm the requirement for NCAM PSA in memory consolidation and separate it from that of NCAM.
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Anticuerpos/farmacología , Reacción de Prevención/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/fisiopatología , Molécula L1 de Adhesión de Célula Nerviosa/inmunología , Ácidos Siálicos/inmunología , Conducta Espacial/efectos de los fármacos , Factores de Edad , Animales , Conducta Animal/efectos de los fármacos , Hipocampo/citología , Inyecciones Intraventriculares/métodos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacosRESUMEN
We describe a Bayesian inference scheme for quantifying the active physiology of neuronal ensembles using local field recordings of synaptic potentials. This entails the inversion of a generative neural mass model of steady-state spectral activity. The inversion uses Expectation Maximization (EM) to furnish the posterior probability of key synaptic parameters and the marginal likelihood of the model itself. The neural mass model embeds prior knowledge pertaining to both the anatomical [synaptic] circuitry and plausible trajectories of neuronal dynamics. This model comprises a population of excitatory pyramidal cells, under local interneuron inhibition and driving excitation from layer IV stellate cells. Under quasi-stationary assumptions, the model can predict the spectral profile of local field potentials (LFP). This means model parameters can be optimised given real electrophysiological observations. The validity of inferences about synaptic parameters is demonstrated using simulated data and experimental recordings from the medial prefrontal cortex of control and isolation-reared Wistar rats. Specifically, we examined the maximum a posteriori estimates of parameters describing synaptic function in the two groups and tested predictions derived from concomitant microdialysis measures. The modelling of the LFP recordings revealed (i) a sensitization of post-synaptic excitatory responses, particularly marked in pyramidal cells, in the medial prefrontal cortex of socially isolated rats and (ii) increased neuronal adaptation. These inferences were consistent with predictions derived from experimental microdialysis measures of extracellular glutamate levels.
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Potenciales de Acción/fisiología , Mapeo Encefálico/métodos , Electroencefalografía/métodos , Modelos Neurológicos , Red Nerviosa/fisiología , Transmisión Sináptica/fisiología , Animales , Teorema de Bayes , Simulación por Computador , HumanosRESUMEN
Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases.
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Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Quimiocinas CXC/metabolismo , Neoplasias Pulmonares/prevención & control , Oligosacáridos/farmacología , Receptores CXCR4/metabolismo , Animales , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Quimiocina CXCL12 , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Heparitina Sulfato/metabolismo , Humanos , Inmunohistoquímica , Radioisótopos de Yodo , Neoplasias Pulmonares/secundario , Ratones , Ratones SCID , Polímeros/metabolismo , Ensayo de Unión Radioligante , Receptores CXCR4/efectos de los fármacos , TinzaparinaRESUMEN
Epidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.
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Andrógenos/farmacología , Proteína BRCA1/genética , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Ovario/metabolismo , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Células Cultivadas , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Progresión de la Enfermedad , Células Epiteliales/metabolismo , Femenino , Citometría de Flujo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Leucina Zippers , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/metabolismo , Ovario/patología , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Neoplásico/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
Isolated arteriovenous fistulas of the posterior orbit occur with exceptional rarity, and their evaluation and management are not well characterized. We describe the clinical presentation and treatment of a spontaneous arteriovenous fistula of the right posterior orbit via a superior ophthalmic vein approach for embolization using platinum detachable coils.
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Fístula Arteriovenosa/terapia , Embolización Terapéutica/instrumentación , Órbita/irrigación sanguínea , Adulto , Angiografía de Substracción Digital , Fístula Arteriovenosa/diagnóstico , Seno Cavernoso/patología , Diseño de Equipo , Estudios de Seguimiento , Humanos , Angiografía por Resonancia Magnética , Masculino , Arteria Maxilar/patología , Arteria Oftálmica/patología , Platino (Metal) , VenasRESUMEN
Transcranial Doppler (TCD) sonography is a new imaging technique allowing for non-invasive evaluation of the intracranial vascular anatomy and cerebral hemodynamics. The recent introduction of echographic contrast agents has significantly increased the sensitivity of TCD for the diagnosis of intracranial vascular lesions. We report a case of giant AComA aneurysm, undetected by color and power TCD, which became visible after echographic contrast administration as a delayed and persistent area of contrast enhancement. Knowledge of atypical or contrast-specific lesion appearances will become important if contrast-enhanced TCD is to be used routinely in the diagnosis of intracranial aneurysms.
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Medios de Contraste , Aneurisma Intracraneal/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/métodos , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance. METHODS: Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12-18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment. RESULTS: Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (chi2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (chi2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk. CONCLUSIONS: These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.
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Pruebas Genéticas/psicología , Neoplasias Ováricas/genética , Neoplasias Ováricas/psicología , Cooperación del Paciente , Adulto , Anciano , Salud de la Familia , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de RiesgoRESUMEN
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7.
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Adenosina Trifosfatasas/metabolismo , Cisteína Endopeptidasas/metabolismo , Complejos Multienzimáticos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Ataxias Espinocerebelosas/metabolismo , Animales , Ataxina-7 , Encéfalo/metabolismo , Células COS , Núcleo Celular/metabolismo , ADN Complementario , Técnica del Anticuerpo Fluorescente , Células HeLa , Humanos , Técnicas para Inmunoenzimas , Péptido Hidrolasas/metabolismo , Péptidos/metabolismo , Pruebas de Precipitina , Complejo de la Endopetidasa Proteasomal , Unión Proteica , Transporte de Proteínas , Ataxias Espinocerebelosas/patología , Técnicas del Sistema de Dos HíbridosRESUMEN
Vertebroplasty is the percutaneous injection of bone cement into a symptomatic fractured vertebral body under fluoroscopic guidance. It is a safe and simple outpatient procedure. We discuss patient selection, the techniques, and the results based on our experience and that of our radiology colleagues.
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Dolor de Espalda/etiología , Cementos para Huesos , Fijación de Fractura/métodos , Cifosis/terapia , Osteoporosis/complicaciones , Polimetil Metacrilato , Fracturas de la Columna Vertebral/terapia , Anciano , Anciano de 80 o más Años , Femenino , Fluoroscopía , Estudios de Seguimiento , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Cuidados Preoperatorios , Fracturas de la Columna Vertebral/etiologíaRESUMEN
The purpose of this study was to correlate the level of cyclooxygenase-2 (COX-2) expression in carcinoma of the cervix with the clinical endpoints: local control, cause-specific survival, and patterns of failure in patients treated with radiotherapy. Formalin-fixed, paraffin-embedded tumor biopsies were stained for COX-2. Clinical factors such as stage, grade, tumor size, pre- and posttreatment hemoglobin level, and radiotherapy dose were also evaluated. Actuarial local control rates and cause-specific survival were determined according to the Kaplan-Meier method. COX-2 distribution staining was the only prognostic factor that was associated with local control and cause-specific survival. High COX-2 distribution staining was associated with decreased local control and decreased cause-specific survival by log rank comparison of Kaplan-Meier survival curves. The 5-year cause-specific survival rates for tumors with low versus high COX-2 distribution values were 90% and 22%, respectively (p = 0.0003). Actuarial pelvic control at 5 years was superior in patients with low COX-2 distribution staining (92%) compared with high staining (42%, p = 0.005). COX-2 staining intensity was found to correlate positively with tumor size (p = 0.02). These findings indicate that increased expression of COX-2 yields reduced pelvic control and cause-specific survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Previously, inhibition of COX-2 has been demonstrated to sensitize tumors to radiation without effect on normal tissue. Taken together, these data may support a novel therapeutic application of COX-2 inhibitors in the treatment of carcinoma of the cervix.