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

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

Depression - A Major Contributor to Poor Quality of Life in Patients With Advanced Cancer

This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Context Quality of life (QoL) and depression are important patient-reported outcomes in cancer care. However, the relative importance of depression severity in predicting QoL remains unclear because of few methodologically sound studies. Objectives To examine whether depression contributes to impairment of QoL irrespective of prognostic factors and symptom burden. Methods A total of 563 patients were included from the European Palliative Care Research Collaborative–Computerized Symptom Assessment Study, an international, multi-center, cross-sectional study. The relative importance of prognostic factors (systemic inflammation [modified Glasgow Prognostic Score—mGPS]), co-morbidities and physical performance (Karnofsky Performance Status), symptom burden (loss of appetite, breathlessness, nausea [Edmonton Symptom Assessment Scale], and pain [Brief Pain Inventory]), and depression severity (Patient Health Questionnaire 9) in predicting Global Health/QoL (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed using hierarchical multiple regression models. Results Fifty-five percent were women, median age was 64 years, 87% had metastatic disease, median Karnofsky Performance Status was 70, and mean global QoL was 50.5 (SD = 23.3). Worse QoL was associated with increased systemic inflammation (mGPS = 1 β = −0.12, P = 0.003; mGPS = 2 β = −0.09, P = 0.023), lower physical performance (β = 0.17, P < 0.001), reduced appetite (β = −0.15, P < 0.001), breathlessness (β = −0.11, P = 0.004), pain (β = −0.14, P = 0.002), and higher depression severity (β = −0.27, P < 0.001). The full model accounted for 29% of the observed variance in QoL scores. The strongest predictor was depression severity, accounting for 5.8% of the variance. Conclusion Depression severity was the strongest single predictor of poorer QoL in this sample of patients with advanced cancer, after accounting for a wide range of clinically relevant variables. Future studies should investigate the contribution of psychosocial variables on QoL. Our findings emphasize the importance of managing depression to achieve the best possible QoL for these patients

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population

Nodavirus colonizes and replicates in the testis of gilthead seabream and European sea bass modulating its immune and reproductive functions

Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to assess local responses. Our in vitro results show that the changes observed on the expression of immune and reproductive genes in the testis of both species are different to those observed upon in vivo infections in most of the casesMINECO and FEDER (AGL2010-20801-C02-01; AGL2010-20801-C02-02; AGL2013-43588-P); Fundación Séneca (04538/GERM/06)Versión del editor4,411