Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

BACKGROUND: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress. METHODS AND RESULTS: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM. CONCLUSIONS AND SIGNIFICANCE: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos

Long non-coding RNAs and cancer: a new frontier of translational research?

Author manuscriptTiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer.RS is supported as a fellow of the TALENTS Programme (7th R&D Framework Programme, Specific Programme: PEOPLE—Marie Curie Actions—COFUND). MIA is supported as a PhD fellow of the FCT (Fundação para a Ciência e Tecnologia), Portugal. GAC is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, as a research scholar by The University of Texas System Regents, and by the Chronic Lymphocytic Leukemia Global Research Foundation. Work in GAC’s laboratory is supported in part by the NIH/ NCI (CA135444); a Department of Defense Breast Cancer Idea Award; Developmental Research Awards from the Breast Cancer, Ovarian Cancer, Brain Cancer, Multiple Myeloma and Leukemia Specialized Programs of Research Excellence (SPORE) grants from the National Institutes of Health; a 2009 Seena Magowitz–Pancreatic Cancer Action Network AACR Pilot Grant; the Laura and John Arnold Foundation and the RGK Foundation

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Predictive models of dairy cow thermal state: a review from a technological perspective

Dairy cattle are particularly sensitive to heat stress due to a higher metabolic rate needed for milk production. In the last decades, global warming, and the dairy production increase in warmer countries, have stimulated the development of a wide range of environmental control systems for dairy farms. Despite their proven effectiveness, the associated energy and water consumption can compromise the viability of dairy farms in many regions, due to the cost and scarcity of these resources. To make these systems more efficient, they should be activated in time to prevent thermal stress and switched off when that risk no longer exists, which must consider environ-mental variables as well as the variables of the animals themselves. Nowadays, there is a wide range of sensors and equipment that support farm routine procedures, and it is possible to measure several variables that, with the aid of algorithms based on predictive models, would allow an-ticipating animals' thermal state. This review summarizes three types of approaches as predictive models: bioclimatic indexes, Machine Learning, and mechanistic models. It also focuses on the application of the current knowledge as algorithms to be used in the management of diverse types of environmental control systems

In vivo systemic toxicity assessment of an oxidized dextrin-based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes

The worldwide incidence of bone disorders is raising, mainly due to ageing population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic-based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels to produce injectable/moldable SBSs. Dextrin, a low-molecular-weight carbohydrate, was used to develop a fully resorbable and injectable hydrogel. It was firstly oxidized with sodium periodate and then cross-linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin-based hydrogel (HG) was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike® (250-500 ?m) to obtain a mouldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling and moulding properties of the formulation, as well as an efficient cohesion of the granules. This article is protected by copyright. All rights reserved.Isabel Pereira was supported by the grant SFRH/BD/ 90066/ 2012 from FCT, Portugal. This work was funded by the project “DEXGELERATION – Advanced solutions for bone regeneration based on dextrin hydrogels” (Norte-07-0202-FEDER-038853) and the project “iBone Therapies – innovative therapies for bone regeneration” (NORTE-01-0247-FEDER-003262). The authors acknowledge the funding from FCT under the scope of the strategic funding of UID/BIO/04469/2013 and UID/BIM/04293/2013 units and COMPETE 2020 (POCI-010145-FEDER-006684), BioTecNorte operation (NORTE-010145-FEDER-000004) and NORTE-01-0145-FEDER-000012 funded by FEDER under the scope of Norte2020—Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Homens e violência conjugal: uma análise de estudos brasileiros Men and conjugal violence: an analysis of Brazilian studies

O estudo analisou qualitativamente 54 textos brasileiros sobre homens e violência conjugal, relacionados a atividades de pesquisa ou de intervenção. Primeiramente caracterizou-se o material quanto aos temas abordados, ao foco principal e ao tipo de texto. A seguir fizeram-se sínteses e análises das principais considerações dos textos a partir dos eixos temáticos encontrados: diferentes inteligibilidades da problemática, magnitude da violência conjugal, sentidos de homens relacionados à violência e intervenções e/ou políticas junto a homens agressores. A análise teve como parâmetro o ramo de discussões nacionais e internacionais que se esforça por ultrapassar a polêmica em torno da definição do problema como "violência de gênero" ou "violência conjugal", cunhando sobretudo o pressuposto de que existem diversos estilos de conjugalidade violenta. Concluiu-se que a maior unanimidade dos estudos é pensar a problemática como questão relacional de gênero. Defendeu-se, por fim, a ideia de que a escolha da melhor abordagem articuladora entre os polos da polêmica ainda demanda mais investigações, com metodologias qualitativas junto a atores de diferentes camadas e grupos sociais. Quanto às intervenções, propõem-se investimentos no maior número possível de alternativas, valorizando a singularidade dos casos.<br>This study consisted of a qualitative analysis of 54 Brazilian texts about men and conjugal violence related to research or intervention activities. Initially, the material was divided up according to the topics under scrutiny, the main focus and the type of text. Analysis and synthesis of the main considerations of the texts, based on the thematic points revealed, was then carried out. This included the different approaches to the problem, the magnitude of conjugal violence, the attitudes of men vis-à-vis violence and interventions and/or policies towards male aggressors. The parameter for the analysis was the national and international debate seeking to overcome the controversy surrounding the definition of the problem as "gender violence" or conjugal violence," essentially fostering the hypothesis of various types of violent conjugal relationships. It was concluded that the unanimous outcome of the study was to view the problem as a gender relationship issue. Lastly, it was argued that the choice of the best approach between the poles of the controversy requires further investigation using qualitative methodologies together with players from different classes and social backgrounds. With respect to further intervention, it was considered necessary to examine a broad gamut of alternatives emphasizing the singular nature of the cases