Etiopathogenesis of ovarian cancer. An inflamm-aging entity?

Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate. The risk/protective factors of ovarian cancer suggest that its etiology is multifactorial. Several factors are involved in age-related increases in carcinogenesis, including the accumulation of senescent cells, inflammaging (a chronic inflammatory state that persists in the elderly), and immunosenescence (aging of the immune system) changes associated with poor immune surveillance. At sites of inflammation, exposure to high levels of inflammatory mediators, such as reactive oxygen species, cytokines, prostaglandins, and growth factors, contributes to increased cell division and genetic and epigenetic changes. These exposure-induced changes promote excessive cell proliferation, increased survival, malignant transformation, and cancer development. Furthermore, the proinflammatory tumor microenvironment contributes to ovarian cancer metastasis and chemoresistance. This narrative review of the literature was carried out to delineate the possible role of inflammaging in the etiopathogenesis of ovarian cancer development. We discuss the current carcinogenic hypotheses, sites of origin, and etiological factors of ovarian cancer. Treatment of inflammation may represent an attractive strategy for both the prevention and therapy of ovarian cancer. © 2022 The Author(s

Organic geochemistry of the Villaviciosa estuary record since 1400 AD (North of Spain)

We have reconstructed the palaeoenvironmental conditions in the Villaviciosa estuary during the last 600 yrs, from the biomarker content (alkanes and alkanoic acids) of the sediment. The amino acid racemization method in ostracodes allowed determining that the sedimentation in the Selorio bay started in 1400 AD. Organic matter was well preserved, although certain microbial activity was interpreted. Three periods were established from the alkane content: 1.- Between 1400 and 1580 AD terrestrial input was dominant; 2.- Between 1580 and 1720 AD there was a major influence of aquatic macrophytes, coinciding with the Little Ice Age, 3.- Between 1720 and 2015 AD there were alternating periods during which land plants or aquatic macrophytes predominated, probably linked to anthropogenic activitiesSe han reconstruido las condiciones paleoambientales de la zona de la ría de Villaviciosa de los últimos 600 años, a partir de los biomarcadores (alcanos y ácidos alcanoicos) presentes en el sedimento. El método de racemización de aminoácidos en ostrácodos ha permitido determinar el inicio de la sedimentación en la ensenada de Selorio, en la ría de Villaviciosa, que comenzó en 1400. La preservación de la materia orgánica es buena, aunque se observa una actividad microbiana importante. A partir de los alcanos se han establecido tres episodios: 1.- Entre 1400 y 1580 predominó el aporte de vegetación terrestre, 2.- Entre 1580 y 1720 hubo una mayor abundancia de macrofitas acuáticas, coincidiendo con la Pequeña Edad del Hielo, 3.- Entre 1720 y 2015, hubo una alternancia de aportes terrestres y de macrofitas acuáticas, posiblemente ligados a la acción antrópic

Estrogen-related genes and postmenopausal osteoporosis risk

Background To date, more than 150 candidate genes related to osteoporosis have been described, but osteoporosis has increasingly been considered a polygenic disease modulated by environmental factors. It is thought that osteoporosis predisposition, pathology, and treatment response depend on the interaction between different genes or between genes and environmental factors. Objective The aim of this study was to evaluate the relationship between the presence of single nucleotide polymorphisms (SNPs) in the estrogen metabolic pathway and the development of osteoporosis and to determine whether this relationship is monogenic or whether interactions between genes exist. Materials and methods A multicentric study with 1980 postmenopausal Spanish women in fi ve Spanish communities was conducted. The women completed a specifi c questionnaire that inquired about risk factors for osteoporosis. Data on participants ’ bone mineral density were obtained with dual-energy X-ray densitometers, and genetic data were obtained from frozen peripheral blood. Results The digenic protection combinations indicated involvement of the wild-type genotype (WT) of the 3 UTR marker for the CYP19A1 gene, the IVS4 marker of the same gene, and the BMP15 and FSHR genes. Among patients who carried two or more of the genotypes considered ‘ risky ’ , the triple combination among markers of the ESR2 and NRIP1 genes with any of the two mutations of the analyzed markers of the BMP15 gene gave a mean T -score value of 2.32 0.91 ( p 0.02). Conclusion Variants of the new candidate genes ( NRIP and BMP15 ) can predispose patients to osteoporosis

Análisis de las roturas del anillo de expansión LD

Presentamos la revisión clínica de 17 casos de roturas del anillo de expansión tipo LD implantados en nuestro Servicio entre 1989 y 1994, de un total de 779 prótesis totales de cadera (2,2%). Se realiza un estudio de las posibles causas que produjeron la rotura del material. Predominaron en pacientes con sobrepeso y con una actividad física intensa. En el análisis de las radiografías destacamos como factores favorecedores de la rotura, la cobertura insuficiente del anillo y su movilización en 16 pacientes (94,1%). Estos hechos obligaron a realizar estudios de elementos finitos y mecánicos que llevaron a la modificación del anillo inicial. El nuevo anillo se ha recubierto de hidroxiapatita y se han trasladado hacia la periferia los orificios para los tornillos. También se ha reducido el espesor y el tamaño de las ranuras entre las aletas.We present the clinical study of 17 breakage of the LD expansive metalling ring, of 779 total hip prosthesis (2,2%) implanted in our Service from 1989 to 1994. An analysis was performed to discover the reasons of the breakage. Dominated in patients with a high activity and overweight. In the roentgenographic analysis of the ring, we emphaise insufficient cover and migration of the ring as predisposing factors in 16 patients (94,1%). For these facts we performed a finite and mechanical element analysis that changed the original ring. The new ring is hyrdoxiapatite coated and the hole for the screws have move periferically. The thickness and the space between slits have been also reduced

Modificaciones funcionales, personales y sociales de las fracturas de la extremidad proximal del fémur en pacientes mayores

Se ha realizado un estudio retrospectivo revisando las historias clínicas de 550 pacientes mayores de 69 años que sufrieron una fractura de cadera durante 1995 y 1996 en Salamanca. Cerca de la mitad de los pacientes estudiados tenían independencia casi total y el 40.22% cambió su tipo de residencia. La mayoría de los pacientes perdieron actividad y se encontraron diferencias estadísticamente significativas en la existencia o no de complicaciones. Casi todas las fracturas ocurrieron tras una caída casual por tropiezos o resbalones. El 57.67% de los pacientes tenían una intensa osteopenia. Alrededor del 25% de los pacientes realizaron rehabilitación, sobre todo los tratados con enclavados endomedulares. La mortalidad fue de 31.37% y se encontraron diferencias estadísticamente significativas al relacionarla con la actividad física previa y postratamiento y el grado de dependencia previa a la fractura. Estos cambios en la función y dependencia, tienen poca influencia en la rehabilitación y mortalidad de los pacientes.Case-history reviews and at-home interviews we used to study retrospectively the 550 patients older than 69 years who suffered a hip fracture between 1995 and 1996 in Salamanca (Spain). The average hospitalization time was 15 days. Almost half of patients were not dependent at all and 40.22% of them moved to another residence. Most patients lost activity, and it was statistically correlated to the adverse events reported. Almost every fracture occurred after a casual fall due to stumbling or sliding. 57.67 % of patients had a severe osteopenia. The most frequent fracture reported was pertrochanteric (44.67%) followed by subcapital, especially those treated with intramedullary nailing. Mortality was 31.37% and statistical differences were found between degree of activity before and after the fracture. These changes in function and type of residence have a scarce influence on rehabilitation and mortality of patients

Biomarkers and inorganic proxies in the paleoenvironmental reconstruction of mires: The importance of landscape in Las Conchas (Asturias, Northern Spain)

We determined the lipid distributions (n-alkanes, n-alkan-2-ones, n-alkanoic acids), total organic carbon (TOC), total nitrogen (TN), Ca/Mg and ash content in Las Conchas mire, a 3.2 m deep bryophyte-dominated mire in Northern Spain covering 8000 cal yr BP. Bog conditions developed in the bottom 20 cm of the profile, and good preservation of organic matter (OM) was inferred from n-alkanoic acid distribution, with the exception of the uppermost 20 cm (last ca. 200 yr). Microbial synthesis of long chain saturated fatty acids from primary OM likely produced a dominance of short chain n-alkanoic acids with a bimodal distribution, as well as the lack of correspondence between the n-alkane and n-alkanoic acid profiles in the upper 20 cm. This was accompanied by an increase in ash content, a decrease in TOC and variation in n-alkane ratios, thereby suggesting significant changes in the mire, namely drainage and transformation to a meadow, in the last ca. 200 yr. The distribution of n-alkan-2-ones indicated an increase in bacterial source from the bottom of the record to 94 cm, whereas their distribution in the upper part could be attributed mainly to plant input and/or the microbial oxidation of n-alkanes. The different n-alkane proxies showed variations, which we interpreted in terms of changes in vegetation (Sphagnum vs. non-Sphagnum dominated phases) during the last 8000 cal yr BP. C23 was the most abundant homolog throughout most of the record, thereby suggesting dominant humid conditions alternating with short drier phases. However, such humid conditions were not linked to paleoclimatic variation but rather to geomorphological characteristics: Las Conchas mire, at the base of the Cuera Range, receives continuous runoff—even during drier periods—which is not necessarily accompanied by additional mineral input to peat, producing the development of Sphagnum moss typical of waterlogged ecotopes and damp habitats. Thus, although geochemical proxies indicated an ombrotrophic regime in the mire, geomorphological characteristics may make a considerable contribution to environmental conditions

APP-derived peptides reflect neurodegeneration in frontotemporal dementia

Altres ajuts: The Catalan frontotemporal initiative (CATFI) is funded by the Health Department of the Government of Catalonia (grant PERIS SLT002/16/00408 to Alberto Lleó and Raquel Sánchez-Valle). This work was also supported by research grants from the CIBERNED Program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, file://www.signalstudy.es), partly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa." This work has also been supported by a "Marató TV3" grant (20141210 to Juan Fortea, 044412 to Rafael Blesa, 20143710 to Ricard Rojas-García and 20143810 to Raquel Sánchez-Valle) and Fundación BBVA (grant to A. Lleó) and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. Ignacio Illán-Gala and Sergi Borrego-Écija are supported by the Rio Hortega grant from "Acción estratégica en Salud 2013-2016" and the European Social Fund. Ignacio Illán-Gala is supported by the Global Brain Health Institute (Atlantic Fellow for Equity in Brain Health). We acknowledge all the participants in this study and all the collaborators of the SPIN cohort. We also acknowledge Soraya Torres and Laia Muñoz for technical assistance. We thank EUROIMMUN for providing Aβ1-38 and Aβ1-40 ELISA assays for this study.Objective: We aimed to investigate the relationship between cerebrospinal fluid levels (CSF) of amyloid precursor protein (APP)-derived peptides related to the amyloidogenic pathway, cortical thickness, neuropsychological performance, and cortical gene expression profiles in frontotemporal lobar degeneration (FTLD)-related syndromes, Alzheimer's disease (AD), and healthy controls. Methods: We included 214 participants with CSF available recruited at two centers: 93 with FTLD-related syndromes, 57 patients with AD, and 64 healthy controls. CSF levels of amyloid β (Aβ)1-42, Aβ1-40, Aβ1-38, and soluble β fragment of APP (sAPPβ) were centrally analyzed. We compared CSF levels of APP-derived peptides between groups and, we studied the correlation between CSF biomarkers, cortical thickness, and domain-specific cognitive composites in each group. Then, we explored the relationship between cortical thickness, CSF levels of APP-derived peptides, and regional gene expression profile using a brain-wide regional gene expression data in combination with gene set enrichment analysis. Results: The CSF levels of Aβ1-40, Aβ1-38, and sAPPβ were lower in the FTLD-related syndromes group than in the AD and healthy controls group. CSF levels of all APP-derived peptides showed a positive correlation with cortical thickness and the executive cognitive composite in the FTLD-related syndromes group but not in the healthy control or AD groups. In the cortical regions where we observed a significant association between cortical thickness and CSF levels of APP-derived peptides, we found a reduced expression of genes related to synaptic function. Interpretation: APP-derived peptides in CSF may reflect FTLD-related neurodegeneration. This observation has important implications as Aβ1-42 levels are considered an indirect biomarker of cerebral amyloidosis

Does ALS-FUS without FUS mutation represent ALS-FET? Report of three cases

Altres ajuts: This study was partially funded by Fundacio Marató de TV3 (grant no. 20143810 to RSV, no. 20141610 to EG and no. 201437.10 to RRG) and Fondo Europeo de Desarrollo Regional (FEDER) (PI16/01673 to JG and PI15/01618 to RRG). We are indebted to the Neurological Tissue Bank of the Biobanc-Hospital Clinic-IDIBAPS, Barcelona, Spain, for data and sample procurement. We thank Sara Charif, Veronica Santiago, Carmen Schweiger, Leire Etxarri and Abel Muñoz for technical assistance

Kernel-based methods for combining information of several frame surveys

A sample selected from a single sampling frame may not represent adequatly the entire population. Multiple frame surveys are becoming increasingly used and popular among statistical agencies and private organizations, in particular in situations where several sampling frames may provide better coverage or can reduce sampling costs for estimating population quantities of interest. Auxiliary information available at the population level is often categorical in nature, so that incorporating categorical and continuous information can improve the efficiency of the method of estimation. Nonparametric regression methods represent a widely used and flexible estimation approach in the survey context. We propose a kernel regression estimator for dual frame surveys that can handle both continuous and categorical data. This methodology is extended to multiple frame surveys. We derive theoretical properties of the proposed methods and numerical experiments indicate that the proposed estimator perform well in practical settings under different scenarios.Ministerio de Economía y CompetitividadConsejería de Economía, Innovación, Ciencia y Emple

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

Somatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response