Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial

Objective To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy

Pathogenicity of nodavirus strains from striped jack Pseudocaranx dentex and Atlantic halibut Hippoglossus hippoglossus, studied by waterborne challenge of yolk-sac larvae of both teleost species

The present study shows that differences in pathogenicity exist among fish nodavirus strains. In challenge trials, a Japanese strain (SJ93Nag) was highly virulent to larvae of the striped jack Pseudocaranx dentex but replication was not detected in larvae of Atlantic halibut Hippoglossus hippoglossus at 6 degrees C. Conversely, a Norwegian nodavirus strain (AH95NorA) that was highly virulent to the Atlantic halibut larvae did not replicate in striped jack larvae at 20 degrees C. Occurrence of the disease viral encephalopathy and retinopathy (VER) and cumulative mortality were significantly different in the 2 species when challenged with the 2 nodavirus strains. The presence of nodavirus in nervous tissue was monitored by immunohistochemical methods. Our results support the view that the genetic diversity among nodavirus strains reflects the existence of different viral phenotypes which may be adapted to infect different host species and/or for replicating at different temperatures. Fish nodaviruses represent surveyable pathogens well suited for studying the relation between viral genotypic and phenotypic properties such as host specificity, temperature optima, neuroinvasiveness and neurovirulence

Vacuolating encephalopathy and retinopathy associated with a nodavirus-like agent:a probable cause of mass mortality of cultured larval and juvenile Atlantic halibut Hippoglossus hippoglossus

Reared larval and juvenile Atlantic halibut Hippoglossus hippoglossus collected during incidences of mass mortality in 2 hatcheries were studied by light and electron microscopy. A vacuolating encephalopathy and retinopathy as well as endocardial lesions were observed. By transmission electron microscopy isometric, spherical, unenveloped virus particles with mean capsid diameters of approximately 25 nm were detected. The virions were found intracytoplasmically in semicrystalline arrays or as membrane-associated aggregates and single particles. Infection could be observed in neurons, astrocytes, oligodendrocytes, microglia/macrophages, lymphocyte-like cells, vascular endothelium, endocardial endothelium, myocardial myocytes and in the mesothelium of the epicardium. Specific immunolabeling was obtained in affected tissues on immunohistochemistry applying primary antisera against nodaviruses isolated from the striped jack Pseudocaranx dentex and the sea bass Dicentrarchus labrax. We suggest that the mortality was caused by a nodavirus-like agent and that this disease of the Atlantic halibut is closely related to diseases termed viral nervous necrosis (VNN), viral encephalopathy and retinopathy, and fish encephalitis, which have been associated with mass mortality in numerous cultured marine teleost species. In Atlantic halibut, viral endocardial lesions were a constant finding, suggesting that viremia may be an important factor in the pathogenesis of the infection

Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study

Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0–19 years) and 218 980 matched population controls, born 1967–2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6–12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8–2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6–3.1) than males (OR = 2.1, 95% CI = 1.9–2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect–cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.publishedVersio

Birth length and weight as predictors of breast cancer prognosis

Background Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients. Methods Information on birth size (weight, length and ponderal index (kg/length (m3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis. Results Breast cancer patients with birth length ≥ 52 cm had nearly twice the risk of dying (hazard ratio, 1.92, 95% confidence interval, 1.09-3.41) from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis. Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival. Conclusions Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms

Patients with advanced cancer and depression report a significantly higher symptom burden than non-depressed patients

OBJECTIVE: Clinical observations indicate that patients with advanced cancer and depression report higher symptom burden than nondepressed patients. This is rarely examined empirically. Study aim was to investigate the association between self-reported depression disorder (DD) and symptoms in patients with advanced cancer controlled for prognostic factors. METHOD: The sample included 935 patients, mean age 62, 52% males, from an international multicentre observational study (European Palliative Care Research Collaborative - Computerised Symptom Assessment and Classification of Pain, Depression and Physical Function). DD was assessed by the Patient Health Questionnaire-9 and scored with Diagnostic and Statistical Manual of Mental Disorder-5 algorithm for major depressive disorder, excluding somatic symptoms. Symptom burden was assessed by summing scores on somatic Edmonton Symptom Assessment Scale (ESAS) symptoms, excluding depression, anxiety, and well-being. Item-by-item scores and symptom burden of those with and without DD were compared using nonparametric Mann-Whitney U tests. The relative importance of sociodemographic, medical, and prognostic factors and DD in predicting symptom burden was assessed by hierarchical, multiple regression analyses. Result Patients with DD reported significantly higher scores on ESAS items and a twofold higher symptom burden compared with those without. Factors associated with higher symptom burden were as follows. DIAGNOSIS: lung (β = 0.15, p < 0.001) or breast cancer (β = 0.08, p < 0.05); poorer prognosis: high C-reactive protein (β = 0.08, p < 0.05), lower Karnofsky Performance Status (β = -0.14, p < 0.001), and greater weight loss (β = -0.15, p < 0.001); taking opioids (β = 0.11, p < 0.01); and having DD (β = 0.23, p < 0.001). The full model explained 18% of the variance in symptom burden. DD explained 4.4% over and above that explained by all the other variables. Significance of results Depression in patients with advanced cancer is associated with higher symptom burden. These results encourage improved routines for identifying and treating those suffering from depression

Frailty modeling of bimodal age-incidence curves of nasopharyngeal carcinoma in low-risk populations

The incidence of nasopharyngeal carcinoma (NPC) varies widely according to age at diagnosis, geographic location, and ethnic background. On a global scale, NPC incidence is common among specific populations primarily living in southern and eastern Asia and northern Africa, but in most areas, including almost all western countries, it remains a relatively uncommon malignancy. Specific to these low-risk populations is a general observation of possible bimodality in the observed age-incidence curves. We have developed a multiplicative frailty model that allows for the demonstrated points of inflection at ages 15–24 and 65–74. The bimodal frailty model has 2 independent compound Poisson-distributed frailties and gives a significant improvement in fit over a unimodal frailty model. Applying the model to population-based cancer registry data worldwide, 2 biologically relevant estimates are derived, namely the proportion of susceptible individuals and the number of genetic and epigenetic events required for the tumor to develop. The results are critically compared and discussed in the context of existing knowledge of the epidemiology and pathogenesis of NPC

The salmon louse genome: Copepod features and parasitic adaptations

Copepods encompass numerous ecological roles including parasites, detrivores and phytoplankton grazers. Nonetheless, copepod genome assemblies remain scarce. Lepeophtheirus salmonis is an economically and ecologically important ectoparasitic copepod found on salmonid fish. We present the 695.4 Mbp L. salmonis genome assembly containing ≈60% repetitive regions and 13,081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics supported annotation and indicated a marked shift in gene expression after host attachment, including apparent downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of genes needed for peroxisome biogenesis, presence of numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite repeated development of resistance against chemical treatments L. salmonis exhibits low numbers of many genes involved in detoxification.publishedVersio