RESUMEN
Interval colorectal cancers (I-CRCs) arise during the interval time period between scheduled colonoscopies. Predicting which patients are at risk of I-CRCs remains an elusive undertaking, but evidence would suggest that most I-CRCs arise from lesions missed on index endoscopy. The procedural factors that lead to missed lesions are numerous and lack consensus in the literature. In Canada, the province of Newfoundland and Labrador has the highest incidence of CRCs. In this study our aim was to examine I-CRCs (3-60 months after last colonoscopy) in NL through a population-level analysis covering 67% of the province from 2001-2018. We estimated the I-CRC rate to be up to 9.3%. Median age of I-CRC diagnosis was 67.1 years with an interval time of 2.9 years. About 57% of these tumors occurred proximal to the splenic flexure, with 53% presenting as local disease. No temporal differences were observed in interval time or tumor distribution. On univariate and multivariable logistical regression, risk of right-sided I-CRC did not correlate to the index colonoscopy indication, bowel preparation quality, size of largest polyp removed, colonoscopy completion rate, or stage at presentation. Improvements in synoptic reporting utilization and national registries are needed to identity risk factors and reduce I-CRC frequency.
Asunto(s)
Neoplasias Colorrectales , Humanos , Anciano , Estudios Retrospectivos , Terranova y Labrador/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Canadá , ColonoscopíaRESUMEN
Human hepatic lipase (hHL) is a cell surface associated enzyme that hydrolyzes triacylglycerols and phospholipids within circulating lipoproteins. We hypothesized that an amino acid sequence mimicking the major heparin binding domain (HBD) of hHL will displace hHL from cell surfaces. To test this hypothesis, we generated a recombinant protein of thioredoxin linked with a cleavable, tagged sequence containing amino acids 442 to 476 of the mature hHL sequence, which contains the major HBD of hHL. The recombinant protein associated with heparin-sepharose, and its peak elution from heparin-sepharose occurred in the presence of 0.5 M NaCl. We cleaved and purified the tagged sequence containing the HBD from the recombinant protein and tested the ability of the peptide to displace full-length hHL from HEK-293 cells. The peptide indeed displaced hHL from cell surfaces, while no significant displacement was observed in the presence of a peptide with a scrambled sequence. Finally, we obtained structural information for the peptide containing the HBD. 1 H- and 15 N-NMR spectra of the peptide indicate the peptide is largely unstructured, although not completely random coil. The addition of heparin to the peptide induced some changes in chemical shift, suggesting changes in peptide structure and/or specific interactions with heparin. Molecular simulations confirm the largely unstructured nature of the isolated peptide, but they also indicate weak tendencies for both α- and ß-structure formation in different parts of the chain. Overall, these data provide a proof-of-principle for the use of mimetic peptides for the displacement of cell surface associated lipases.
Asunto(s)
Heparina/metabolismo , Lipasa/química , Lipasa/metabolismo , Péptidos/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Biomimética , Membrana Celular/metabolismo , Simulación por Computador , Células HEK293 , Humanos , Modelos Moleculares , Péptidos/química , Péptidos/aislamiento & purificación , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Tiorredoxinas/metabolismoRESUMEN
A door-to-door population-based epidemiological study of the prevalence of migraine and headache in a sample of 3,246 people older than 15 years of age was carried out in Cuzco, a high-altitude town in the Peruvian Andes, located at 3,380 meters. Among the 3,246 screened people, there were 172 cases of migraine and 930 cases of headache, yielding a crude 1-year prevalence of 5.3% for migraine (2.3% among men and 7.8% among women) and 28.7% for headache (17.5% among men and 38.2% among women). Our results suggest that migraine prevalence in Cuzco is close to that of other developing countries, whereas headache prevalence may be higher than in other developing countries. Multivariate logistic regression suggested that both migraine and headache were related to the female sex, age, and anxiety and/or depression. This study suggests that migraine is a relatively common disorder in Cuzco, but does not show any difference which could significantly related to altitude. In contrast, our results suggest that headache may be more frequent at high altitude than at sea level.