RESUMO
Colon cancer screening occurs at younger ages than osteoporosis screening. Bone density measurements using virtual colonoscopy performed for colon cancer screening can provide an early warning sign of patients at potential risk for osteoporosis-related fractures. Earlier identification may improve treatment and potentially fracture prevention. INTRODUCTION: Opportunistic osteoporosis screening with computed tomography colonography (CTC) offers an opportunity to capitalize on earlier colorectal cancer screening to identify patients at risk of future fractures. The purpose of this study is to evaluate 10-year fracture and specifically hip fracture risk based on Hounsfield units (HU) obtained from CTC. METHODS: We identified all CTC scans between 2004 and 2007 of patients 40 years and older with 10 years minimum follow-up. Hounsfield units were measured within the proximal femur and fractures identified via worldwide military records. Patients were stratified into two cohorts based on the presence or lack of a fracture in the wrist, spine, hip, or proximal humerus. Hounsfield unit measurements were compared between groups using Student's t test and the HU threshold was calculated that best approximated an 80% sensitivity to optimally screen patients for fracture risk. The odds ratio, negative predictive value, 10-year incidence of fracture, and survival curves were calculated. RESULTS: We identified 3711 patients with 183 fractures over 10 years. The HU threshold that corresponded with an 80% sensitivity to identify fractures was 112 HU. The negative predictive value (NPV) for overall fractures and hip fractures was over 97%. The 10-year fracture incidence was higher in patients below 112 HU compared to those above for both overall fractures (6.3% vs 1.7%) and hip fractures (2.7% vs 0.07%). The 112 HU threshold corresponds with an odds ratio for overall fracture and hip fractures of 2.5 (95% confidence interval (CI), 1.7-3.6) and 24.5 (95% CI, 3.3-175.5), respectively. CONCLUSION: In the 10 years following CTC, patients who experienced a fracture had lower hip HU. Decreasing HU on CTC may be an early warning sign of fracture potential.
Assuntos
Fraturas do Fêmur , Osteoporose , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Densidade Óssea , Fraturas do Fêmur/epidemiologia , Fêmur , Humanos , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Medição de RiscoRESUMO
INTRODUCTION: Inflammation is a key aspect of glioblastoma multiforme (GBM) although it remains unclear how it contributes to GBM pathogenesis. Inflammasomes are intracellular multi-protein complexes that are involved in innate immunity and are activated by cellular stress, principally in macrophages. This study examined the expression of inflammasome-associated genes in GBM, particularly absent in melanoma 2 (AIM2). METHODS: Tissue samples from surgically-resected GBM tumors (n = 10) were compared to resected brain specimens from patients with epilepsy (age- and sex-matched Other Disease Controls (ODC, n=5)) by qRT-PCR, western blotting and immunofluorescence. Gene expression studies in human astrocytoma U251 cells were performed and the effects of deleting the absent in melanoma 2 (AIM2) gene using the CRISPR-Cas9 system were analyzed. RESULTS: GBM tissues showed significantly elevated expression of multiple immune (CD3E, CD163, CD68, MX1, ARG1) and inflammasome (AIM2, NLRP1, IL18, CASP1, and IL-33) genes compared to ODC tissues, without induction of IL1B, IFNG or TNFA. An insert-containing AIM2 variant transcript was highly expressed in GBM tissues and in U251 cells. AIM2 immunoreactivity was concentrated in the tumor core in the absence of PCNA immunodetection and showed a predominant 52 kDa immunoreactive band on western blot. Deletion of AIM2 resulted in significantly enhanced proliferation of U251 cells, which also displayed increased resistance to temozolomide treatment. CONCLUSIONS: GBM tumors express a distinct profile of inflammasome-associated genes in a tumor-specific manner. AIM2 expression in tumor cells suppressed cell proliferation while also conferring increased susceptibility to contemporary GBM therapy.
Assuntos
Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Glioblastoma/patologia , Inflamassomos/metabolismo , Inflamação/patologia , Biomarcadores Tumorais , Estudos de Casos e Controles , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Inflamassomos/genética , Inflamação/genética , Inflamação/metabolismo , RNA Interferente Pequeno/genética , Células Tumorais CultivadasAssuntos
Lobectomia Temporal Anterior/métodos , Encéfalo/anormalidades , Epilepsia/cirurgia , Proteínas Associadas aos Microtúbulos , Adulto , Córtex Cerebral/anormalidades , Córtex Cerebral/cirurgia , Proteínas do Domínio Duplacortina , Epilepsia/genética , Feminino , Humanos , Masculino , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/cirurgia , Neuropeptídeos/genética , Resultado do TratamentoRESUMO
The maximun permissible fluence is proposed as a practical concept in radiological monitoring of photon fields. It is virtually this concept that is used for monitoring neutron fields. The practicability of designing instruments with a required response function over a large energy range is examined. Cavity isonisation theory is employed to examine the effect of gas filling, wall material, chamber size and wall thickness on response function and the optimum parameters for the design of an ionisation chamber are thus identified. An experimental chamber of parameters close to the optimum has been constructed and its response compared with the response calculated from cavity ionisation theory. It is concluded that it is possible to design an instrument, the energy response of which follows the maximum permissible fluence. The approach and data in this paper will facilitate any necessary design changes which would arise in the event of national regulation being modified.
