Biomimetic device and foreign body reaction cooperate for efficient tumour cell capture in murine advanced ovarian cancer

Metastasis is facilitated by the formation of pre-metastatic niches through the remodelling of the extracellular matrix (ECM) promoted by haematopoietic and stromal cells. The impact of these primed sites is pronounced for intraperitoneal metastases, where the cavity-exposed ECM supports the attachment of the disseminating tumour cells. Likewise, implantation of biomaterial scaffolds influences metastatic progression systemically through a foreign body reaction (FBR). In this study, we integrated the concept of creating an artificial niche to capture tumour cells actively disseminating in the peritoneal cavity with a therapeutic strategy modulating the interactions of metastatic cells with the ECM. The aim was to transform a disseminated disease into a focal disease. For this, we designed and developed a ‘biomimetic’ ECM composed of a nonresorbable three-dimensional scaffold with collagen coating and characterized the FBR to the implanted biomaterial. We also analysed the safety of the implanted devices and their ability to capture tumour cells in different murine preclinical models of advanced ovarian cancer. Implantation of the biomimetic devices resulted in an initial inflammatory reaction that transformed progressively into a fibrous connective tissue response. The adhesive capabilities of the scaffold were improved with the ancillary effect of the FBR and showed clinical utility in terms of the efficacy of capture of tumour cells, disease focalization and survival benefit. These results demonstrated the performance and safety of this ‘biomimetic’ ECM in preclinical models of advanced ovarian cancer. Translated into the clinical setting, this new therapeutic strategy represents the possibility for control of peritoneal carcinomatosis upon primary ovarian debulking surgery and to expand the percentage of patients who are candidates for second rescue surgeries at the time of relapse.This work was supported by Nasasbiotec

Magnetic detection of sentinel lymph node in papillary thyroid carcinoma: The MAGIC-PAT study results

Introduction: Despite the controversy concerning sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC), successful detection rates can be achieved by radioguidance and vital dyeing. However, the drawbacks in both techniques are notable. Magnetic-guided SLNB (mSLNB) using superparamagnetic iron oxide (SPIO) nanoparticles is appealing as an alternative procedure. Materials and Methods: mSLNB using the Sentimag-Sienna System ® , total thyroidectomy and central compartment dissection (CCD) were performed on all PTC patients. Lymph node involvement was assessed by postoperative pathological examination. Results: From 2014 to 2016, 33 consecutive patients with PTC were enrolled in the study. A total of 20 patients met the eligibility. mSLNB succeeded in 16 patients, with a detection rate of 80%. A median of two SLN per patient were detected. A median of 10.5 non-sentinel lymph nodes (NSLN) from CCD were examined. Among the patients, 56.25% (9/16) had no metastatic nodes, while 12.5% (2/16) had exclusively SLN involvement. No false negative cases were found. The agreement between SLN and NSLN status was 87.5%. The prediction of NSLN involvement by SLN status showed 100% sensitivity, 81.8% specificity, 71.4% PPV and 100% NPV. Subsequently, mSLNB and the final pathological analysis would discriminate 43.75% (7/16) of patients who would certainly benefit from CCD whilst 56.25% of the total would confirm an unnecessary lymphadenectomy and avoid morbidity. Conclusion: mSLNB showed satisfactory performance in PTC with clinical-negative nodes. We have shown mSLNB to be a good predictor of central compartment status that can improve the staging and management of PTC patients

Species occurrence of ticks in South America, and interactions with biotic and abiotic traits

The datasets of records of the distribution of ticks and their hosts are invaluable tools to understand the phylogenetic patterns of evolution of ticks and the abiotic traits to which they are associated. Such datasets require an exhaustive collection of bibliographical references. In most cases, it is necessary the confirmation of reliable identification of ticks, together with an update of the scientific names of the vertebrate hosts. These data are not easily available, because many records were published in the so-called “grey literature”. Herein, we introduced the Dataset of Ticks in South America, a repository that collates data on 4,764 records of ticks (4,124 geo-referenced) with a special reference to an extra 2,370 records of ticks on cattle, together with a set of abiotic traits, curated from satellite-derived information over the complete target region. The dataset includes details of the phylogenetic relationships of the species of hosts, providing researchers with both biotic and abiotic traits that drive the distribution and evolution of ticks in South America.publishersversionpublishe

Low genetic diversity of the only clade of the tick rhipicephalus microplus in the neotropics

This study addresses the variability of the mitochondrial cytochrome oxidase subunit I (COI) and 16S rDNA (16S), and nuclear internal transcriber spacer ITS2 (ITS2) genes in a set of field-collected samples of the cattle tick, Rhipicephalus microplus (Canestrini, 1888), and in geo-referenced sequences obtained from GenBank. Since the tick is currently considered to be a complex of cryptic taxa in several regions of the world, the main aims of the study are (i) to provide evidence of the clades of the tick present in the Neotropics, (ii) to explore if there is an effect of climate traits on the divergence rates of the target genes, and (iii) to check for a relationship between geographical and genetic distance among populations (the closest, the most similar, meaning for slow spread). We included published sequences of Rhipicephalus annulatus (Nearctic, Afrotropical, and Mediterranean) and R. microplus (Afrotropical, Indomalayan) to fully characterize the Neotropical populations (total: 74 16S, 44 COI, and 49 ITS2 sequences included in the analysis). Only the clade A of R. microplus spread in the Nearctic–Neotropics. Both the K and Lambda’s statistics, two measures of phylogenetic signal, support low divergence rates of the tested genes in populations of R. microplus in the Neotropics. These tests demonstrate that genetic diversity of the continental populations does not correlate either with the geographic distance among samples or with environmental variables. The low variability of these genes may be due to a combination of factors like (i) the recent introduction of the tick in the Neotropics, (ii) a large, effective, and fast exchange of populations, and (iii) a low effect of climate on the evolution rates of the target genes. These results have implications for the ecological studies and control of cattle tick infestations

Exposure of zebra mussels to extracorporeal shock waves demonstrates formation of new mineralized tissue inside and outside the focus zone

The success rate of extracorporeal shock wave therapy (ESWT) for fracture nonunions in human medicine (i.e. radiographic union at 6 months after ESWT) is only approximately 75%. Detailed knowledge regarding the underlying mechanisms that induce biocalcification after ESWT is limited. We analyzed the biological response within mineralized tissue of a new invertebrate model organism, the zebra mussel Dreissena polymorpha, after exposure with extracorporeal shock waves (ESWs). Mussels were exposed to ESWs with positive energy density of 0.4 mJ/mm(2) (A) or were sham exposed (B). Detection of newly calcified tissue was performed by exposing the mussels to fluorescent markers. Two weeks later, the A-mussels showed a higher mean fluorescence signal intensity within the shell zone than the B-mussels (P<0.05). Acoustic measurements revealed that the increased mean fluorescence signal intensity within the shell of the A-mussels was independent of the size and position of the focal point of the ESWs. These data demonstrate that induction of bio-calcification after ESWT may not be restricted to the region of direct energy transfer of ESWs into calcified tissue. The results of the present study are of relevance for better understanding of the molecular and cellular mechanisms that induce formation of new mineralized tissue after ESWT

One Health Approach to Identify Research Needs on Rhipicephalus microplus Ticks in the Americas

We aim to provide a harmonized view of the factors that affect the survival and promote the spread of R. microplus in the Neotropics, approaching its different facets of biology, ecology, distribution, and control. We review the interactions among environmental niche, landscape fragmentation, vegetal coverage (abiotic traits), and the biotic aspects of its ecology (abundance of domesticated or wild competent hosts), proposing emerging areas of research. We emphasize a holistic view integrating an economically and ecologically sustainable control of infestations and transmitted pathogens by R. microplus in the Neotropics. Examples of research link the trends of climate, the composition of the community of hosts, the landscape features, and a tailored management based on ecological grounds. Our view is that factors driving the spread of R. microplus are complex and deeply interrelated, something that has been seldom considered in control strategies. The effects of climate may affect the dynamics of wildlife or the landscape composition, promoting new patterns of seasonal activity of the tick, or its spread into currently free areas. In this paper we encourage a One Health approach highlighting the main aspects governing the components of the tick’s life cycle and its interactions with livestock and wild animals.Nuestro objetivo es ofrecer una visión armonizada de los factores que afectan a la supervivencia y promueven la propagación de R. microplus en el Neotrópico, abordando sus diferentes facetas de biología, ecología, distribución y control. Revisamos las interacciones entre el nicho ambiental, la fragmentación del paisaje la cobertura vegetal (rasgos abióticos), y los aspectos bióticos de su ecología (abundancia de hospedadores domesticados domésticos o silvestres competentes), proponiendo áreas emergentes de investigación. Hacemos hincapié en una visión holística integrando un control económica y ecológicamente sostenible de las infestaciones y los patógenos transmitidos patógenos transmitidos por R. microplus en el Neotrópico. Los ejemplos de investigación vinculan las tendencias del clima, la composición de la comunidad de hospedadores, las características del paisaje y una gestión adaptada basada en motivos ecológicos. Nuestra opinión es que los factores que impulsan la propagación de R. microplus son complejos y profundamente interrelacionados, algo que rara vez se ha tenido en cuenta en las estrategias de control. Los efectos del Los efectos del clima pueden afectar a la dinámica de la vida silvestre o a la composición del paisaje, promoviendo nuevos patrones de actividad estacional de la garrapata, o su propagación en zonas actualmente libres. En este artículo se fomenta un enfoque de En este documento fomentamos un enfoque de "salud", destacando los principales aspectos que rigen los componentes del ciclo de vida de la garrapata y sus interacciones con el ganado y los animales salvajes. sus interacciones con el ganado y los animales salvajes

Perception of Ticks and Tick-Borne Diseases Worldwide

In this comprehensive review study, we addressed the challenge posed by ticks and tick-borne diseases (TBDs) with growing incidence affecting human and animal health worldwide. Data and perspectives were collected from different countries and regions worldwide, including America, Europe, Africa, Asia, and Oceania. The results updated the current situation with ticks and TBD and how it is perceived by society with information bias and gaps. The study reinforces the importance of multidisciplinary and international collaborations to advance in the surveillance, communication and proposed future directions to address these challenges

A Comparison of Connected Speech Tasks for Detecting Early Alzheimer's Disease and Mild Cognitive Impairment Using Natural Language Processing and Machine Learning

Alzheimer’s disease (AD) has a long pre-clinical period, and so there is a crucial need for early detection, including of Mild Cognitive Impairment (MCI). Computational analysis of connected speech using Natural Language Processing and machine learning has been found to indicate disease and could be utilized as a rapid, scalable test for early diagnosis. However, there has been a focus on the Cookie Theft picture description task, which has been criticized. Fifty participants were recruited – 25 healthy controls (HC), 25 mild AD or MCI (AD+MCI) – and these completed five connected speech tasks: picture description, a conversational map reading task, recall of an overlearned narrative, procedural recall and narration of a wordless picture book. A high-dimensional set of linguistic features were automatically extracted from each transcript and used to train Support Vector Machines to classify groups. Performance varied, with accuracy for HC vs. AD+MCI classification ranging from 62% using picture book narration to 78% using overlearned narrative features. This study shows that, importantly, the conditions of the speech task have an impact on the discourse produced, which influences accuracy in detection of AD beyond the length of the sample. Further, we report the features important for classification using different tasks, showing that a focus on the Cookie Theft picture description task may narrow the understanding of how early AD pathology impacts speech

Pathogens and host immunity in the ancient human oral cavity.

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past

The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: A report from the Euro Heart Survey on Coronary Revascularisation

Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice