SEOM clinical guideline in ovarian cancer (2020)

Despite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer remains the leading cause of death from gynecologic cancer. In the last decade, there have been important advances both in systemic and surgical treatment. However, there is no doubt that the incorporation of PARP inhibitors as maintenance after the response to platinum-based chemotherapy, first in recurrent disease and recently also in first line, will change the natural history of the disease. The objective of this guide is to summarize the current evidence for the diagnosis, treatment, and follow-up of ovarian cancer, and to provide evidence-based recommendations for clinical practice

Determination of cutoff values on computed tomography and magnetic resonance images for the diagnosis of atlantoaxial instability in small-breed dogs.

OBJECTIVE To determine cutoff values for the diagnosis of atlantoaxial instability (AAI) based on cross-sectional imaging in small-breed dogs. STUDY DESIGN Retrospective multicenter study. SAMPLE POPULATION Client-owned dogs (n = 123) and 28 cadavers. METHODS Dogs were assigned to three groups: a control group, a "potentially unstable" group, and an AAI-affected group, according to imaging findings and clinical signs. The ventral compression index (VCI), cranial translation ratio (CTR), C1-C2 overlap, C1-C2 angle, atlantoaxial distance, basion-dens interval, dens-to-axis length ratio (DALR), power ratio, and clivus canal angles were measured on CT or T2-weighted magnetic resonance (MR) images. Receiver operating characteristic (ROC) analysis was performed to define cutoff values in flexed (≥25°) and extended (<25°) head positions. RESULTS Cutoff values for the VCI of ≥0.16 in extended and ≥0.2 in flexed head positions were diagnostic for AAI (sensitivity of 100% and 100%, specificity of 94.54% and 96.67%, respectively). Cutoff values for the other measurements were defined with a lower sensitivity (75%-96%) and specificity (70%-97%). A combination of the measurements did not increase the sensitivity and specificity compared with the VCI as single measurement. CONCLUSION Cutoff values for several imaging measurements were established with good sensitivity and specificity. The VCI, defined as the ratio between the ventral and dorsal atlantodental interval, had the highest sensitivity and specificity in both head positions. CLINICAL SIGNIFICANCE The use of defined cutoff values allows an objective diagnosis of AAI in small-breed dogs. The decision for surgical intervention, however, should remain based on a combination of clinical and imaging findings

The number of matchings in random graphs

We study matchings on sparse random graphs by means of the cavity method. We first show how the method reproduces several known results about maximum and perfect matchings in regular and Erdos-Renyi random graphs. Our main new result is the computation of the entropy, i.e. the leading order of the logarithm of the number of solutions, of matchings with a given size. We derive both an algorithm to compute this entropy for an arbitrary graph with a girth that diverges in the large size limit, and an analytic result for the entropy in regular and Erdos-Renyi random graph ensembles.Comment: 17 pages, 6 figures, to be published in Journal of Statistical Mechanic

Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Analysis of anti-RNA polymerase III antibody positive systemic sclerosis suggests altered GPATCH2L and CTNND2 expression in scleroderma renal crisis

OBJECTIVE: Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti RNA polymerase III antibody (ARA) autoantibodies. We explore genetic susceptibility and altered protein expression in renal biopsy specimens in ARA positive SRC. METHODS: ARA-positive patients (n=99) with at least 5 years' follow-up (49% with a history of SRC) were selected from a well-characterised SSc cohort (n=2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, nine SNPs were chosen for validation in a separate cohort of 256 ARA+ patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort. RESULTS: Analysis of 641,489 SNPs suggested association of POU2F1 (rs2093658; 1.98x10-5), CTNND2 (rs1859082; p=7.14 x 10-5), HECW2 (rs16849716; p=1.2 x 10-4) and GPATCH2L (rs935332; p=4.92 x 10-5) with SRC. Furthermore, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (p=0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (p=0.026), and glomerular expression of CTNND2 (p=0.026) in SRC samples (n=8) compared with normal human kidney controls (n=8), despite absence of any genetic replication for the associated SNP. CONCLUSION: Increased expression of two candidate proteins GPATCH2L and CTNND2 in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L this may reflect genetic susceptibility in ARA positive SSc based upon 2 independent cohorts

A cohort study of the effects of older adult care dependence upon household economic functioning, in Peru, Mexico and China

BACKGROUND: While links between disability and poverty are well established, there have been few longitudinal studies to clarify direction of causality, particularly among older adults in low and middle income countries. We aimed to study the effect of care dependence among older adult residents on the economic functioning of their households, in catchment area survey sites in Peru, Mexico and China. METHODS: Households were classified from the evolution of the needs for care of older residents, over two previous community surveys, as 'incident care', 'chronic care' or 'no care', and followed up three years later to ascertain economic outcomes (household income, consumption, economic strain, satisfaction with economic circumstances, healthcare expenditure and residents giving up work or education to care). RESULTS: Household income did not differ between household groups. However, income from paid work (Pooled Count Ratio pCR 0.88, 95% CI 0.78-1.00) and government transfers (pCR 0.80, 95% CI 0.69-0.93) were lower in care households. Consumption was 12% lower in chronic care households (pCR 0.88, 95% CI 0.77-0.99). Household healthcare expenditure was higher (pCR 1.55, 95% CI 1.26-1.90), and catastrophic healthcare spending more common (pRR 1.64, 95% CI 1.64-2.22) in care households. CONCLUSIONS: While endogeneity cannot be confidently excluded as an explanation for the findings, this study indicates that older people's needs for care have a discernable impact on household economics, controlling for baseline indicators of long-term economic status. Although living, typically, in multigenerational family units, older people have not featured prominently in global health and development agendas. Population ageing will rapidly increase the number of households where older people live, and their societal significance. Building sustainable long-term care systems for the future will require some combination of improved income security in old age; incentivisation of informal care through compensation for direct and opportunity costs; and development of community care services to support, and, where necessary, supplement or substitute the central role of informal caregivers

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders